Journal articles: 'RNA epitranscriptome'

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Xia, Zhen, Min Tang, Jiayan Ma, et al. "Epitranscriptomic editing of the RNA N6-methyladenosine modification by dCasRx conjugated methyltransferase and demethylase." Nucleic Acids Research 49, no. 13 (2021): 7361–74. http://dx.doi.org/10.1093/nar/gkab517.

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Abstract N6-methyladenosine (m6A) is a common modification on endogenous RNA transcripts in mammalian cells. Technologies to precisely modify the RNA m6A levels at specific transcriptomic loci empower interrogation of biological functions of epitranscriptomic modifications. Here, we developed a bidirectional dCasRx epitranscriptome editing platform composed of a nuclear-localized dCasRx conjugated with either a methyltransferase, METTL3, or a demethylase, ALKBH5, to manipulate methylation events at targeted m6A sites. Leveraging this platform, we specifically and efficiently edited m6A modifications at targeted sites, reflected in gene expression and cell proliferation. We employed the dCasRx epitranscriptomic editor system to elucidate the molecular function of m6A-binding proteins YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3), revealing that YTHDFs promote m6A-mediated mRNA degradation. Collectively, our dCasRx epitranscriptome perturbation platform permits site-specific m6A editing for delineating of functional roles of individual m6A modifications in the mammalian epitranscriptome.

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Evke, Sara, Qishan Lin, Juan Andres Melendez, and Thomas John Begley. "Epitranscriptomic Reprogramming Is Required to Prevent Stress and Damage from Acetaminophen." Genes 13, no. 3 (2022): 421. http://dx.doi.org/10.3390/genes13030421.

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Epitranscriptomic marks, in the form of enzyme catalyzed RNA modifications, play important gene regulatory roles in response to environmental and physiological conditions. However, little is known with respect to how acute toxic doses of pharmaceuticals influence the epitranscriptome. Here we define how acetaminophen (APAP) induces epitranscriptomic reprogramming and how the writer Alkylation Repair Homolog 8 (Alkbh8) plays a key gene regulatory role in the response. Alkbh8 modifies tRNA selenocysteine (tRNASec) to translationally regulate the production of glutathione peroxidases (Gpx’s) and other selenoproteins, with Gpx enzymes known to play protective roles during APAP toxicity. We demonstrate that APAP increases toxicity and markers of damage, and decreases selenoprotein levels in Alkbh8 deficient mouse livers, when compared to wildtype. APAP also promotes large scale reprogramming of many RNA marks comprising the liver tRNA epitranscriptome including: 5-methoxycarbonylmethyluridine (mcm5U), isopentenyladenosine (i6A), pseudouridine (Ψ), and 1-methyladenosine (m1A) modifications linked to tRNASec and many other tRNA’s. Alkbh8 deficiency also leads to wide-spread epitranscriptomic dysregulation in response to APAP, demonstrating that a single writer defect can promote downstream changes to a large spectrum of RNA modifications. Our study highlights the importance of RNA modifications and translational responses to APAP, identifies writers as key modulators of stress responses in vivo and supports the idea that the epitranscriptome may play important roles in responses to pharmaceuticals.

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Tang, Yujiao, Kunqi Chen, Bowen Song, et al. "m6A-Atlas: a comprehensive knowledgebase for unraveling the N6-methyladenosine (m6A) epitranscriptome." Nucleic Acids Research 49, no. D1 (2020): D134—D143. http://dx.doi.org/10.1093/nar/gkaa692.

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Abstract N 6-Methyladenosine (m6A) is the most prevalent RNA modification on mRNAs and lncRNAs. It plays a pivotal role during various biological processes and disease pathogenesis. We present here a comprehensive knowledgebase, m6A-Atlas, for unraveling the m6A epitranscriptome. Compared to existing databases, m6A-Atlas features a high-confidence collection of 442 162 reliable m6A sites identified from seven base-resolution technologies and the quantitative (rather than binary) epitranscriptome profiles estimated from 1363 high-throughput sequencing samples. It also offers novel features, such as; the conservation of m6A sites among seven vertebrate species (including human, mouse and chimp), the m6A epitranscriptomes of 10 virus species (including HIV, KSHV and DENV), the putative biological functions of individual m6A sites predicted from epitranscriptome data, and the potential pathogenesis of m6A sites inferred from disease-associated genetic mutations that can directly destroy m6A directing sequence motifs. A user-friendly graphical user interface was constructed to support the query, visualization and sharing of the m6A epitranscriptomes annotated with sites specifying their interaction with post-transcriptional machinery (RBP-binding, microRNA interaction and splicing sites) and interactively display the landscape of multiple RNA modifications. These resources provide fresh opportunities for unraveling the m6A epitranscriptomes. m6A-Atlas is freely accessible at: www.xjtlu.edu.cn/biologicalsciences/atlas.

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Schaefer, Matthias R. "The Regulation of RNA Modification Systems: The Next Frontier in Epitranscriptomics?" Genes 12, no. 3 (2021): 345. http://dx.doi.org/10.3390/genes12030345.

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RNA modifications, long considered to be molecular curiosities embellishing just abundant and non-coding RNAs, have now moved into the focus of both academic and applied research. Dedicated research efforts (epitranscriptomics) aim at deciphering the underlying principles by determining RNA modification landscapes and investigating the molecular mechanisms that establish, interpret and modulate the information potential of RNA beyond the combination of four canonical nucleotides. This has resulted in mapping various epitranscriptomes at high resolution and in cataloguing the effects caused by aberrant RNA modification circuitry. While the scope of the obtained insights has been complex and exciting, most of current epitranscriptomics appears to be stuck in the process of producing data, with very few efforts to disentangle cause from consequence when studying a specific RNA modification system. This article discusses various knowledge gaps in this field with the aim to raise one specific question: how are the enzymes regulated that dynamically install and modify RNA modifications? Furthermore, various technologies will be highlighted whose development and use might allow identifying specific and context-dependent regulators of epitranscriptomic mechanisms. Given the complexity of individual epitranscriptomes, determining their regulatory principles will become crucially important, especially when aiming at modifying specific aspects of an epitranscriptome both for experimental and, potentially, therapeutic purposes.

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Schwartz, Schraga. "Cracking the epitranscriptome." RNA 22, no. 2 (2016): 169–74. http://dx.doi.org/10.1261/rna.054502.115.

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Imbriano, Carol, Viviana Moresi, Silvia Belluti, et al. "Epitranscriptomics as a New Layer of Regulation of Gene Expression in Skeletal Muscle: Known Functions and Future Perspectives." International Journal of Molecular Sciences 24, no. 20 (2023): 15161. http://dx.doi.org/10.3390/ijms242015161.

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Epitranscriptomics refers to post-transcriptional regulation of gene expression via RNA modifications and editing that affect RNA functions. Many kinds of modifications of mRNA have been described, among which are N6-methyladenosine (m6A), N1-methyladenosine (m1A), 7-methylguanosine (m7G), pseudouridine (Ψ), and 5-methylcytidine (m5C). They alter mRNA structure and consequently stability, localization and translation efficiency. Perturbation of the epitranscriptome is associated with human diseases, thus opening the opportunity for potential manipulations as a therapeutic approach. In this review, we aim to provide an overview of the functional roles of epitranscriptomic marks in the skeletal muscle system, in particular in embryonic myogenesis, muscle cell differentiation and muscle homeostasis processes. Further, we explored high-throughput epitranscriptome sequencing data to identify RNA chemical modifications in muscle-specific genes and we discuss the possible functional role and the potential therapeutic applications.

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Chen, Kunqi, Zhen Wei, Hui Liu, et al. "Enhancing Epitranscriptome Module Detection from m6A-Seq Data Using Threshold-Based Measurement Weighting Strategy." BioMed Research International 2018 (June 14, 2018): 1–15. http://dx.doi.org/10.1155/2018/2075173.

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To date, with well over 100 different types of RNA modifications associated with various molecular functions identified on diverse types of RNA molecules, the epitranscriptome has emerged to be an important layer for gene expression regulation. It is of crucial importance and increasing interest to understand how the epitranscriptome is regulated to facilitate different biological functions from a global perspective, which may be carried forward by finding biologically meaningful epitranscriptome modules that respond to upstream epitranscriptome regulators and lead to downstream biological functions; however, due to the intrinsic properties of RNA molecules, RNA modifications, and relevant sequencing technique, the epitranscriptome profiled from high-throughput sequencing approaches often suffers from various artifacts, jeopardizing the effectiveness of epitranscriptome modules identification when using conventional approaches. To solve this problem, we developed a convenient measurement weighting strategy, which can largely tolerate the artifacts of high-throughput sequencing data. We demonstrated on real data that the proposed measurement weighting strategy indeed brings improved performance in epitranscriptome module discovery in terms of both module accuracy and biological significance. Although the new approach is integrated with Euclidean distance measurement in a hierarchical clustering scenario, it has great potential to be extended to other distance measurements and algorithms as well for addressing various tasks in epitranscriptome analysis. Additionally, we show for the first time with rigorous statistical analysis that the epitranscriptome modules are biologically meaningful with different GO functions enriched, which established the functional basis of epitranscriptome modules, fulfilled a key prerequisite for functional characterization, and deciphered the epitranscriptome and its regulation.

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Ma, Jiongming, Bowen Song, Zhen Wei, et al. "m5C-Atlas: a comprehensive database for decoding and annotating the 5-methylcytosine (m5C) epitranscriptome." Nucleic Acids Research 50, no. D1 (2021): D196—D203. http://dx.doi.org/10.1093/nar/gkab1075.

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Abstract 5-Methylcytosine (m5C) is one of the most prevalent covalent modifications on RNA. It is known to regulate a broad variety of RNA functions, including nuclear export, RNA stability and translation. Here, we present m5C-Atlas, a database for comprehensive collection and annotation of RNA 5-methylcytosine. The database contains 166 540 m5C sites in 13 species identified from 5 base-resolution epitranscriptome profiling technologies. Moreover, condition-specific methylation levels are quantified from 351 RNA bisulfite sequencing samples gathered from 22 different studies via an integrative pipeline. The database also presents several novel features, such as the evolutionary conservation of a m5C locus, its association with SNPs, and any relevance to RNA secondary structure. All m5C-atlas data are accessible through a user-friendly interface, in which the m5C epitranscriptomes can be freely explored, shared, and annotated with putative post-transcriptional mechanisms (e.g. RBP intermolecular interaction with RNA, microRNA interaction and splicing sites). Together, these resources offer unprecedented opportunities for exploring m5C epitranscriptomes. The m5C-Atlas database is freely accessible at https://www.xjtlu.edu.cn/biologicalsciences/m5c-atlas.

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Wanowska, Elzbieta, Alexis McFeely, and Joanna Sztuba-Solinska. "The Role of Epitranscriptomic Modifications in the Regulation of RNA–Protein Interactions." BioChem 2, no. 4 (2022): 241–59. http://dx.doi.org/10.3390/biochem2040017.

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Epitranscriptome refers to post-transcriptional modifications to RNA and their associated regulatory factors that can govern changes in an organism’s cells in response to various environmental stimuli. Recent studies have recognized over 170 distinct chemical signatures in RNA, and the list keeps expanding. These modifications are hypothesized to have roles beyond simply fine-tuning the structure and function of RNA, as studies have linked them to various infectious and noninfectious diseases in humans. Dedicated cellular machinery comprising of RNA-binding proteins (RBPs) that can write, erase, and read these modifications drives the regulation of the epitranscriptomic code, and as such influences RNA metabolism and homeostasis. Equally, perturbations in the function of RBPs may disrupt RNA processing, further implicating them in pathogenesis. As such, the mechanisms underlying RNA modifications and their association with RBPs are emerging areas of interest within the field of biomedicine. This review focuses on understanding epitranscriptomic modifications, their effects on RNA–RBPs interactions, and their influence on cellular processes.

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Chatterjee, Biswanath, Che-Kun James Shen, and Pritha Majumder. "RNA Modifications and RNA Metabolism in Neurological Disease Pathogenesis." International Journal of Molecular Sciences 22, no. 21 (2021): 11870. http://dx.doi.org/10.3390/ijms222111870.

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The intrinsic cellular heterogeneity and molecular complexity of the mammalian nervous system relies substantially on the dynamic nature and spatiotemporal patterning of gene expression. These features of gene expression are achieved in part through mechanisms involving various epigenetic processes such as DNA methylation, post-translational histone modifications, and non-coding RNA activity, amongst others. In concert, another regulatory layer by which RNA bases and sugar residues are chemically modified enhances neuronal transcriptome complexity. Similar RNA modifications in other systems collectively constitute the cellular epitranscriptome that integrates and impacts various physiological processes. The epitranscriptome is dynamic and is reshaped constantly to regulate vital processes such as development, differentiation and stress responses. Perturbations of the epitranscriptome can lead to various pathogenic conditions, including cancer, cardiovascular abnormalities and neurological diseases. Recent advances in next-generation sequencing technologies have enabled us to identify and locate modified bases/sugars on different RNA species. These RNA modifications modulate the stability, transport and, most importantly, translation of RNA. In this review, we discuss the formation and functions of some frequently observed RNA modifications—including methylations of adenine and cytosine bases, and isomerization of uridine to pseudouridine—at various layers of RNA metabolism, together with their contributions to abnormal physiological conditions that can lead to various neurodevelopmental and neurological disorders.

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Dr., HumnaAyyaz Butt, Javaria Syed Dr., Asma Sajid Dr., and Hamid Jugg Dr. "EXAMINE THE MASS SPECTROMETRY METHOD FOR TESTING THE EPITRANSCRIPTOME IN CELLULAR LYSATES." Journal For Innovative Development in Pharmaceutical and Technical Science 2, no. 11 (2019): 110–19. https://doi.org/10.5281/zenodo.4433679.

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New findings in the field of epitranscriptomics have led to resurgence in the study of modified nucleic acids in RNA. Current mass spectrometry methods for the study of the epitranscriptome lack key information on the state of modified nucleotides in RNA and cellular lysates. Presented here is the first report of modified nucleotides in RNA and the cell, and provides the first reported method for the untargeted analysis of these compounds using HILIC-HRMS. We utilized a novel extraction method to measure both the bound and unbound modified nucleotides in a single sample. This method also provides separation of many modified nucleoside species. MS-FINDER software was used to provide in silico structure predictions for the creation of fragmentation rules for separation of methylated modified nucleotides on the MS2 level. Annotated here are 12 modified nucleotide species and 20 nucleosides across RNA types and cell lines.

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Morales Shnaider, Frank A., Coston Eddings, Jennifer Simpson, Bakhos A. Tannous, and Norman Chiu. "Abstract B038: Accurate quantitative profiling of rna modifications and their associations with glioblastoma." Cancer Research 84, no. 5_Supplement_1 (2024): B038. http://dx.doi.org/10.1158/1538-7445.brain23-b038.

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Abstract Every chemical group that is added to one of the canonical ribonucleotides, i.e., RNA modification, in a specific transcript can potentially alter the RNA folding as well as the RNA-protein interactions. Hence, RNA modifications are considered as post-transcriptional regulators for RNA splicing, RNA stability, and translation, just to name a few. Today, 170+ different RNA modifications have been identified, but only half a dozen of them are linked to glioblastoma (GBM). On the other hand, other RNA biology studies indicated the interplays between RNA modifications within a specific epitranscriptome could play a regulatory role in cellular activities. Although suitable methods for profiling RNA modifications in a specific epitranscriptome are available, the lack of ribonucleoside standards has prohibited the accurate quantification of each detectable RNA modification. To address this analytical challenge, our group has recently developed a mass spectrometric method that can achieve accurate quantitative profiling of untargeted RNA modifications without using any standards. Using the developed method, all the RNA modifications in patient-derived GBM cell lines could be profiled with high accuracy. In total, 31 different RNA modifications were detected in the GBM epitranscriptomes. By comparing with the profile detected in healthy human brain tissues, a unique set of upregulated RNA modifications is associated with the development of GBM. These findings are supported by the upregulated gene expression data obtained from GBM patients that are available in The Cancer Genome Atlas program. Citation Format: Frank A Morales Shnaider, Coston Eddings, Jennifer Simpson, Bakhos A. Tannous, Norman Chiu. Accurate quantitative profiling of rna modifications and their associations with glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr B038.

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Li, Xiaoyu, Xushen Xiong, and Chengqi Yi. "Epitranscriptome sequencing technologies: decoding RNA modifications." Nature Methods 14, no. 1 (2016): 23–31. http://dx.doi.org/10.1038/nmeth.4110.

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del Valle-Morales, Daniel, Patricia Le, Michela Saviana, et al. "The Epitranscriptome in miRNAs: Crosstalk, Detection, and Function in Cancer." Genes 13, no. 7 (2022): 1289. http://dx.doi.org/10.3390/genes13071289.

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The epitranscriptome encompasses all post-transcriptional modifications that occur on RNAs. These modifications can alter the function and regulation of their RNA targets, which, if dysregulated, result in various diseases and cancers. As with other RNAs, miRNAs are highly modified by epitranscriptomic modifications such as m6A methylation, 2′-O-methylation, m5C methylation, m7G methylation, polyuridine, and A-to-I editing. miRNAs are a class of small non-coding RNAs that regulates gene expression at the post-transcriptional level. miRNAs have gathered high clinical interest due to their role in disease, development, and cancer progression. Epitranscriptomic modifications alter the targeting, regulation, and biogenesis of miRNAs, increasing the complexity of miRNA regulation. In addition, emerging studies have revealed crosstalk between these modifications. In this review, we will summarize the epitranscriptomic modifications—focusing on those relevant to miRNAs—examine the recent crosstalk between these modifications, and give a perspective on how this crosstalk expands the complexity of miRNA biology.

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Saletore, Yogesh, Selina Chen-Kiang, and Christopher E. Mason. "Novel RNA regulatory mechanisms revealed in the epitranscriptome." RNA Biology 10, no. 3 (2013): 342–46. http://dx.doi.org/10.4161/rna.23812.

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O'Connell, Mary. "RNA modification and the epitranscriptome; the next frontier." RNA 21, no. 4 (2015): 703–4. http://dx.doi.org/10.1261/rna.050260.115.

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Yang, Chengfeng, and Zhishan Wang. "The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis." International Journal of Molecular Sciences 23, no. 19 (2022): 11830. http://dx.doi.org/10.3390/ijms231911830.

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Metals are common toxic environmental pollutants. Acute or chronic exposure to metal pollutants causes severe adverse health effects in animals and humans, such as developmental retardation, abnormal metabolism, and disorders of cardiovascular, neurologic, respiratory, reproductive, and urologic systems. Moreover, several metals (arsenic, cadmium, chromium, and nickel) are classified as potent Group I carcinogens and cause various types of cancer in humans. Although the toxicity and carcinogenicity of metal pollutants are well recognized, the underlying mechanisms have not been clearly defined. The epitranscriptome includes all kinds of chemical modifications of all forms of RNA molecules inside a cell. Recent progresses in demonstrating the reversible pattern of RNA modifications and their roles in physiology and pathogenesis represent a breakthrough in the field of RNA biology and function study. The epitranscriptomic study is now an exciting emerging field in toxicology research. While few studies have been conducted so far to determine the epitranscriptomic effects of metal pollutants, they offer novel insights for understanding the mechanisms of metal toxicity and carcinogenesis. The goal of this review is to discuss recent studies on the epitranscriptomic effects of metals and propose some thoughts for future studies in the field.

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Tan, Kar-Tong, Ling-Wen Ding, Chan-Shuo Wu, Daniel G. Tenen, and Henry Yang. "Repurposing RNA sequencing for discovery of RNA modifications in clinical cohorts." Science Advances 7, no. 32 (2021): eabd2605. http://dx.doi.org/10.1126/sciadv.abd2605.

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The study of RNA modifications in large clinical cohorts can reveal relationships between the epitranscriptome and human diseases, although this is especially challenging. We developed ModTect (https://github.com/ktan8/ModTect), a statistical framework to identify RNA modifications de novo by standard RNA-sequencing with deletion and mis-incorporation signals. We show that ModTect can identify both known (N1-methyladenosine) and previously unknown types of mRNA modifications (N2,N2-dimethylguanosine) at nucleotide-resolution. Applying ModTect to 11,371 patient samples and 934 cell lines across 33 cancer types, we show that the epitranscriptome was dysregulated in patients across multiple cancer types and was additionally associated with cancer progression and survival outcomes. Some types of RNA modification were also more disrupted than others in patients with cancer. Moreover, RNA modifications contribute to multiple types of RNA-DNA sequence differences, which unexpectedly escape detection by Sanger sequencing. ModTect can thus be used to discover associations between RNA modifications and clinical outcomes in patient cohorts.

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Miano, Valentina, Azzurra Codino, Luca Pandolfini, and Isaia Barbieri. "The non-coding epitranscriptome in cancer." Briefings in Functional Genomics 20, no. 2 (2021): 94–105. http://dx.doi.org/10.1093/bfgp/elab003.

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Abstract Post-synthesis modification of biomolecules is an efficient way of regulating and optimizing their functions. The human epitranscriptome includes a variety of more than 100 modifications known to exist in all RNA subtypes. Modifications of non-coding RNAs are particularly interesting since they can directly affect their structure, stability, interaction and function. Indeed, non-coding RNAs such as tRNA and rRNA are the most modified RNA species in eukaryotic cells. In the last 20 years, new functions of non-coding RNAs have been discovered and their involvement in human disease, including cancer, became clear. In this review, we will present the evidence connecting modifications of different non-coding RNA subtypes and their role in cancer.

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Chen, Kunqi, Bowen Song, Yujiao Tang, et al. "RMDisease: a database of genetic variants that affect RNA modifications, with implications for epitranscriptome pathogenesis." Nucleic Acids Research 49, no. D1 (2020): D1396—D1404. http://dx.doi.org/10.1093/nar/gkaa790.

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Abstract Deciphering the biological impacts of millions of single nucleotide variants remains a major challenge. Recent studies suggest that RNA modifications play versatile roles in essential biological mechanisms, and are closely related to the progression of various diseases including multiple cancers. To comprehensively unveil the association between disease-associated variants and their epitranscriptome disturbance, we built RMDisease, a database of genetic variants that can affect RNA modifications. By integrating the prediction results of 18 different RNA modification prediction tools and also 303,426 experimentally-validated RNA modification sites, RMDisease identified a total of 202,307 human SNPs that may affect (add or remove) sites of eight types of RNA modifications (m6A, m5C, m1A, m5U, Ψ, m6Am, m7G and Nm). These include 4,289 disease-associated variants that may imply disease pathogenesis functioning at the epitranscriptome layer. These SNPs were further annotated with essential information such as post-transcriptional regulations (sites for miRNA binding, interaction with RNA-binding proteins and alternative splicing) revealing putative regulatory circuits. A convenient graphical user interface was constructed to support the query, exploration and download of the relevant information. RMDisease should make a useful resource for studying the epitranscriptome impact of genetic variants via multiple RNA modifications with emphasis on their potential disease relevance. RMDisease is freely accessible at: www.xjtlu.edu.cn/biologicalsciences/rmd.

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Cleynen, Alice, Agin Ravindran, Dipti Talaulikar, Eduardo Eyras, and Nikolay Shirokikh. "Defining Therapeutic Epitranscriptome of Multiple Myeloma for Accurate Subtyping and Personalized Prognostics." Blood 144, Supplement 1 (2024): 4652. https://doi.org/10.1182/blood-2024-204896.

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Background: Multiple Myeloma (MM) is a heterogeneous disease, with risk classification (standard risk SR and high risk HR) mostly defined by cytogenetic changes. RNA covalent modifications (collectively addressed as the epitranscriptome) have recently emerged as key signatures of cancer progression, with RNA modification writer and eraser inhibitors being clinically trialed. For example, inhibitor of FTO, an eraser for N6-methyladenosine (m6A), was shown to synergistically suppress MM for mouse models in combined treatment. However, we still lack accurate, nucleotide-resolved landscape of the main RNA modifications, such as m6A, 5-methylcytosine (m5C), N4-acetylcytosine (ac4C) and pseudouridine (pU) in MM, which substantially restricts refined diagnostic, prognostic and drug development opportunities. Here we provide this missing information by investigating the epitranscriptomic signatures of SR and HR MM. Methods: To obtain the isoform-resolved information about concurrent presence of m6A, m5C, ac4C and pU in native MM RNA at single-molecule, single-nucleotide resolution transcriptome-wide, we employed nanopore-based direct RNA sequencing (DRS). DRS was performed on purified tumor cells from three SR and three HR MM patients. Data were analyzed for the modification sites and stoichiometry using in-house developed SWARM software. Modifications were filtered based on probability thresholds controlling the false discovery rate. MM genetic markers and cytogenetic subtypes were analyzed for the epitranscriptome asscociations. Results: For all modification types with the exception of m5C in standard-risk patients, we observed a significantly higher modification rate in the light and heavy chains of the immunoglobulin (Ig) genes compared to other mRNAs: m6A was increased by a 3.6 fold (σ 1.7) in HR patients and 1.4 fold (σ 0.7) in SR; m5C by a 5.4 (σ 6.4) and 0.71 (σ 0.1) fold; pU by a 4.2 (σ 3) and 3 (σ 1.4) fold; and ac4C by a 8.1 (σ 2.7) and 2.8 (σ 3) fold, respectively. While it is known that the variable segment of the Ig chains are highly prone to mutations, we show here that the constant regions instead have a significantly higher rate of modification, regardless of the chain type. More specifically, ac4C and m5C rates are the highest in Ig light chains, in particular in the constant region. In HR MM, m6A and pU are the highest in the Ig light constant segments while in SR MM patients, they are the highest in the Ig variable light segments. Importantly, other MM prognostic genes such as B2M or JUND also globally exhibited a higher modification rate compared to the background mRNA average (m5C 5.6 and 9.6; ac4C 2 and 9.6; m6A 4.1 and 24; and pU 1 and 2.2 fold higher, respectively). Yet across all tested RNA, SR patients were characterized by a higher m5C and ac4C modification rate (compared to HR patients, ~4 fold) with nonetheless lower ac4C stoichiometry in modified sites, and a lower m6A and pU rate (~2 fold). HR patients displayed a higher expression of the main modification writer enzymes. Interrogation focused on ribosomal (r)RNA further indicates specific sites of differential modification stoichiometry that have previously been linked to reduced tumor-suppressor expression and aggressive tumor phenotypes in other cancer types. Conclusion: Our data describe a diverse and rich epitranscriptomic landscape in Multiple Myeloma, strongly associating with the MM subtypes and risk. Association of poor prognostic with higher modification deposition together with specific rRNA modification pattern differences indicate that the epitranscriptome plays an important role in the biology of Multiple Myeloma, and suggest that epitranscriptome-resolved DRS data will provide more accurate subtyping and reveal new pathways and targets of drug response.

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Li, Xiaoyu, Xushen Xiong, and Chengqi Yi. "Erratum: Epitranscriptome sequencing technologies: decoding RNA modifications." Nature Methods 14, no. 3 (2017): 323. http://dx.doi.org/10.1038/nmeth0317-323c.

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McCaffrey, Anton P. "RNA Epitranscriptome: Role of the 5' Cap." Genetic Engineering & Biotechnology News 39, no. 5 (2019): 59, 61. http://dx.doi.org/10.1089/gen.39.05.17.

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Jantsch, Michael F., and Matthias R. Schaefer. "“Mining the Epitranscriptome: Detection of RNA editing and RNA modifications”." Methods 156 (March 2019): 1–4. http://dx.doi.org/10.1016/j.ymeth.2019.02.016.

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Baquero-Perez, Belinda, Daryl Geers, and Juana Díez. "From A to m6A: The Emerging Viral Epitranscriptome." Viruses 13, no. 6 (2021): 1049. http://dx.doi.org/10.3390/v13061049.

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There are over 100 different chemical RNA modifications, collectively known as the epitranscriptome. N6-methyladenosine (m6A) is the most commonly found internal RNA modification in cellular mRNAs where it plays important roles in the regulation of the mRNA structure, stability, translation and nuclear export. This modification is also found in viral RNA genomes and in viral mRNAs derived from both RNA and DNA viruses. A growing body of evidence indicates that m6A modifications play important roles in regulating viral replication by interacting with the cellular m6A machinery. In this review, we will exhaustively detail the current knowledge on m6A modification, with an emphasis on its function in virus biology.

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Shoaib, Yasira, Babar Usman, Hunseung Kang, and Ki-Hong Jung. "Epitranscriptomics: An Additional Regulatory Layer in Plants’ Development and Stress Response." Plants 11, no. 8 (2022): 1033. http://dx.doi.org/10.3390/plants11081033.

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Epitranscriptomics has added a new layer of regulatory machinery to eukaryotes, and the advancement of sequencing technology has revealed more than 170 post-transcriptional modifications in various types of RNAs, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and long non-coding RNA (lncRNA). Among these, N6-methyladenosine (m6A) and N5-methylcytidine (m5C) are the most prevalent internal mRNA modifications. These regulate various aspects of RNA metabolism, mainly mRNA degradation and translation. Recent advances have shown that regulation of RNA fate mediated by these epitranscriptomic marks has pervasive effects on a plant’s development and responses to various biotic and abiotic stresses. Recently, it was demonstrated that the removal of human-FTO-mediated m6A from transcripts in transgenic rice and potatoes caused a dramatic increase in their yield, and that the m6A reader protein mediates stress responses in wheat and apple, indicating that regulation of m6A levels could be an efficient strategy for crop improvement. However, changing the overall m6A levels might have unpredictable effects; therefore, the identification of precise m6A levels at a single-base resolution is essential. In this review, we emphasize the roles of epitranscriptomic modifications in modulating molecular, physiological, and stress responses in plants, and provide an outlook on epitranscriptome engineering as a promising tool to ensure food security by editing specific m6A and m5C sites through robust genome-editing technology.

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Quin, Jaclyn, Jiří Sedmík, Dragana Vukić, Anzer Khan, Liam P. Keegan, and Mary A. O’Connell. "ADAR RNA Modifications, the Epitranscriptome and Innate Immunity." Trends in Biochemical Sciences 46, no. 9 (2021): 758–71. http://dx.doi.org/10.1016/j.tibs.2021.02.002.

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Grozhik, Anya V., and Samie R. Jaffrey. "Distinguishing RNA modifications from noise in epitranscriptome maps." Nature Chemical Biology 14, no. 3 (2018): 215–25. http://dx.doi.org/10.1038/nchembio.2546.

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Arzumanian, Viktoriia A., Georgii V. Dolgalev, Ilya Y. Kurbatov, Olga I. Kiseleva, and Ekaterina V. Poverennaya. "Epitranscriptome: Review of Top 25 Most-Studied RNA Modifications." International Journal of Molecular Sciences 23, no. 22 (2022): 13851. http://dx.doi.org/10.3390/ijms232213851.

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The alphabet of building blocks for RNA molecules is much larger than the standard four nucleotides. The diversity is achieved by the post-transcriptional biochemical modification of these nucleotides into distinct chemical entities that are structurally and functionally different from their unmodified counterparts. Some of these modifications are constituent and critical for RNA functions, while others serve as dynamic markings to regulate the fate of specific RNA molecules. Together, these modifications form the epitranscriptome, an essential layer of cellular biochemistry. As of the time of writing this review, more than 300 distinct RNA modifications from all three life domains have been identified. However, only a few of the most well-established modifications are included in most reviews on this topic. To provide a complete overview of the current state of research on the epitranscriptome, we analyzed the extent of the available information for all known RNA modifications. We selected 25 modifications to describe in detail. Summarizing our findings, we describe the current status of research on most RNA modifications and identify further developments in this field.

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Morales, David Rodríguez, Sarah Rennie, and Shizuka Uchida. "Benchmarking RNA Editing Detection Tools." BioTech 12, no. 3 (2023): 56. http://dx.doi.org/10.3390/biotech12030056.

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RNA, like DNA and proteins, can undergo modifications. To date, over 170 RNA modifications have been identified, leading to the emergence of a new research area known as epitranscriptomics. RNA editing is the most frequent RNA modification in mammalian transcriptomes, and two types have been identified: (1) the most frequent, adenosine to inosine (A-to-I); and (2) the less frequent, cysteine to uracil (C-to-U) RNA editing. Unlike other epitranscriptomic marks, RNA editing can be readily detected from RNA sequencing (RNA-seq) data without any chemical conversions of RNA before sequencing library preparation. Furthermore, analyzing RNA editing patterns from transcriptomic data provides an additional layer of information about the epitranscriptome. As the significance of epitranscriptomics, particularly RNA editing, gains recognition in various fields of biology and medicine, there is a growing interest in detecting RNA editing sites (RES) by analyzing RNA-seq data. To cope with this increased interest, several bioinformatic tools are available. However, each tool has its advantages and disadvantages, which makes the choice of the most appropriate tool for bench scientists and clinicians difficult. Here, we have benchmarked bioinformatic tools to detect RES from RNA-seq data. We provide a comprehensive view of each tool and its performance using previously published RNA-seq data to suggest recommendations on the most appropriate for utilization in future studies.

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Tűzesi, Ágota, Susannah Hallal, Laveniya Satgunaseelan, Michael E. Buckland, and Kimberley L. Alexander. "Understanding the Epitranscriptome for Avant-Garde Brain Tumour Diagnostics." Cancers 15, no. 4 (2023): 1232. http://dx.doi.org/10.3390/cancers15041232.

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RNA modifications are diverse, dynamic, and reversible transcript alterations rapidly gaining attention due to their newly defined RNA regulatory roles in cellular pathways and pathogenic mechanisms. The exciting emerging field of ‘epitranscriptomics’ is predominantly centred on studying the most abundant mRNA modification, N6-methyladenine (m6A). The m6A mark, similar to many other RNA modifications, is strictly regulated by so-called ‘writer’, ‘reader’, and ‘eraser’ protein species. The abundance of genes coding for the expression of these regulator proteins and m6A levels shows great potential as diagnostic and predictive tools across several cancer fields. This review explores our current understanding of RNA modifications in glioma biology and the potential of epitranscriptomics to develop new diagnostic and predictive classification tools that can stratify these highly complex and heterogeneous brain tumours.

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Schaefer, Matthias, Utkarsh Kapoor, and Michael F. Jantsch. "Understanding RNA modifications: the promises and technological bottlenecks of the ‘epitranscriptome’." Open Biology 7, no. 5 (2017): 170077. http://dx.doi.org/10.1098/rsob.170077.

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The discovery of mechanisms that alter genetic information via RNA editing or introducing covalent RNA modifications points towards a complexity in gene expression that challenges long-standing concepts. Understanding the biology of RNA modifications represents one of the next frontiers in molecular biology. To this date, over 130 different RNA modifications have been identified, and improved mass spectrometry approaches are still adding to this list. However, only recently has it been possible to map selected RNA modifications at single-nucleotide resolution, which has created a number of exciting hypotheses about the biological function of RNA modifications, culminating in the proposition of the ‘epitranscriptome’. Here, we review some of the technological advances in this rapidly developing field, identify the conceptual challenges and discuss approaches that are needed to rigorously test the biological function of specific RNA modifications.

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Sikorski, Vilbert, Pasi Karjalainen, Daria Blokhina, et al. "Epitranscriptomics of Ischemic Heart Disease—The IHD-EPITRAN Study Design and Objectives." International Journal of Molecular Sciences 22, no. 12 (2021): 6630. http://dx.doi.org/10.3390/ijms22126630.

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Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.

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Takeda, Yu, Ryota Chijimatsu, Andrea Vecchione, et al. "Impact of One-Carbon Metabolism-Driving Epitranscriptome as a Therapeutic Target for Gastrointestinal Cancer." International Journal of Molecular Sciences 22, no. 14 (2021): 7278. http://dx.doi.org/10.3390/ijms22147278.

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One-carbon (1C) metabolism plays a key role in biological functions linked to the folate cycle. These include nucleotide synthesis; the methylation of DNA, RNA, and proteins in the methionine cycle; and transsulfuration to maintain the redox condition of cancer stem cells in the tumor microenvironment. Recent studies have indicated that small therapeutic compounds affect the mitochondrial folate cycle, epitranscriptome (RNA methylation), and reactive oxygen species reactions in cancer cells. The epitranscriptome controls cellular biochemical reactions, but is also a platform for cell-to-cell interaction and cell transformation. We present an update of recent advances in the study of 1C metabolism related to cancer and demonstrate the areas where further research is needed. We also discuss approaches to therapeutic drug discovery using animal models and propose further steps toward developing precision cancer medicine.

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Morena, Francesco, Chiara Argentati, Martina Bazzucchi, Carla Emiliani, and Sabata Martino. "Above the Epitranscriptome: RNA Modifications and Stem Cell Identity." Genes 9, no. 7 (2018): 329. http://dx.doi.org/10.3390/genes9070329.

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Jiang, Qingfei, Leslie A. Crews, Frida Holm, and Catriona H. M. Jamieson. "RNA editing-dependent epitranscriptome diversity in cancer stem cells." Nature Reviews Cancer 17, no. 6 (2017): 381–92. http://dx.doi.org/10.1038/nrc.2017.23.

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37

Helm, Mark, and Yuri Motorin. "Detecting RNA modifications in the epitranscriptome: predict and validate." Nature Reviews Genetics 18, no. 5 (2017): 275–91. http://dx.doi.org/10.1038/nrg.2016.169.

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Manavski, Nikolay, Alexandre Vicente, Wei Chi, and Jörg Meurer. "The Chloroplast Epitranscriptome: Factors, Sites, Regulation, and Detection Methods." Genes 12, no. 8 (2021): 1121. http://dx.doi.org/10.3390/genes12081121.

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Modifications in nucleic acids are present in all three domains of life. More than 170 distinct chemical modifications have been reported in cellular RNAs to date. Collectively termed as epitranscriptome, these RNA modifications are often dynamic and involve distinct regulatory proteins that install, remove, and interpret these marks in a site-specific manner. Covalent nucleotide modifications-such as methylations at diverse positions in the bases, polyuridylation, and pseudouridylation and many others impact various events in the lifecycle of an RNA such as folding, localization, processing, stability, ribosome assembly, and translational processes and are thus crucial regulators of the RNA metabolism. In plants, the nuclear/cytoplasmic epitranscriptome plays important roles in a wide range of biological processes, such as organ development, viral infection, and physiological means. Notably, recent transcriptome-wide analyses have also revealed novel dynamic modifications not only in plant nuclear/cytoplasmic RNAs related to photosynthesis but especially in chloroplast mRNAs, suggesting important and hitherto undefined regulatory steps in plastid functions and gene expression. Here we report on the latest findings of known plastid RNA modifications and highlight their relevance for the post-transcriptional regulation of chloroplast gene expression and their role in controlling plant development, stress reactions, and acclimation processes.

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Huang, Daiyun, Bowen Song, Jingjue Wei, Jionglong Su, Frans Coenen, and Jia Meng. "Weakly supervised learning of RNA modifications from low-resolution epitranscriptome data." Bioinformatics 37, Supplement_1 (2021): i222—i230. http://dx.doi.org/10.1093/bioinformatics/btab278.

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Abstract Motivation Increasing evidence suggests that post-transcriptional ribonucleic acid (RNA) modifications regulate essential biomolecular functions and are related to the pathogenesis of various diseases. Precise identification of RNA modification sites is essential for understanding the regulatory mechanisms of RNAs. To date, many computational approaches for predicting RNA modifications have been developed, most of which were based on strong supervision enabled by base-resolution epitranscriptome data. However, high-resolution data may not be available. Results We propose WeakRM, the first weakly supervised learning framework for predicting RNA modifications from low-resolution epitranscriptome datasets, such as those generated from acRIP-seq and hMeRIP-seq. Evaluations on three independent datasets (corresponding to three different RNA modification types and their respective sequencing technologies) demonstrated the effectiveness of our approach in predicting RNA modifications from low-resolution data. WeakRM outperformed state-of-the-art multi-instance learning methods for genomic sequences, such as WSCNN, which was originally designed for transcription factor binding site prediction. Additionally, our approach captured motifs that are consistent with existing knowledge, and visualization of the predicted modification-containing regions unveiled the potentials of detecting RNA modifications with improved resolution. Availability implementation The source code for the WeakRM algorithm, along with the datasets used, are freely accessible at: https://github.com/daiyun02211/WeakRM Supplementary information Supplementary data are available at Bioinformatics online.

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Wang, Jin, Bing Liang Alvin Chew, Yong Lai, et al. "Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA." Nucleic Acids Research 47, no. 20 (2019): e130-e130. http://dx.doi.org/10.1093/nar/gkz751.

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Abstract Chemical modification of transcripts with 5′ caps occurs in all organisms. Here, we report a systems-level mass spectrometry-based technique, CapQuant, for quantitative analysis of an organism's cap epitranscriptome. The method was piloted with 21 canonical caps—m7GpppN, m7GpppNm, GpppN, GpppNm, and m2,2,7GpppG—and 5 ‘metabolite’ caps—NAD, FAD, UDP-Glc, UDP-GlcNAc, and dpCoA. Applying CapQuant to RNA from purified dengue virus, Escherichia coli, yeast, mouse tissues, and human cells, we discovered new cap structures in humans and mice (FAD, UDP-Glc, UDP-GlcNAc, and m7Gpppm6A), cell- and tissue-specific variations in cap methylation, and high proportions of caps lacking 2′-O-methylation (m7Gpppm6A in mammals, m7GpppA in dengue virus). While substantial Dimroth-induced loss of m1A and m1Am arose with specific RNA processing conditions, human lymphoblast cells showed no detectable m1A or m1Am in caps. CapQuant accurately captured the preference for purine nucleotides at eukaryotic transcription start sites and the correlation between metabolite levels and metabolite caps.

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Kvolik Pavić, Ana, Josipa Čonkaš, Ivan Mumlek, Vedran Zubčić, and Petar Ozretić. "Clinician’s Guide to Epitranscriptomics: An Example of N1-Methyladenosine (m1A) RNA Modification and Cancer." Life 14, no. 10 (2024): 1230. http://dx.doi.org/10.3390/life14101230.

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Epitranscriptomics is the study of modifications of RNA molecules by small molecular residues, such as the methyl (-CH3) group. These modifications are inheritable and reversible. A specific group of enzymes called “writers” introduces the change to the RNA; “erasers” delete it, while “readers” stimulate a downstream effect. Epitranscriptomic changes are present in every type of organism from single-celled ones to plants and animals and are a key to normal development as well as pathologic processes. Oncology is a fast-paced field, where a better understanding of tumor biology and (epi)genetics is necessary to provide new therapeutic targets and better clinical outcomes. Recently, changes to the epitranscriptome have been shown to be drivers of tumorigenesis, biomarkers, and means of predicting outcomes, as well as potential therapeutic targets. In this review, we aimed to give a concise overview of epitranscriptomics in the context of neoplastic disease with a focus on N1-methyladenosine (m1A) modification, in layman’s terms, to bring closer this omics to clinicians and their future clinical practice.

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42

Guo, Zhenxing, Daoyu Duan, Wen Tang, et al. "magpie: A power evaluation method for differential RNA methylation analysis in N6-methyladenosine sequencing." PLOS Computational Biology 20, no. 2 (2024): e1011875. http://dx.doi.org/10.1371/journal.pcbi.1011875.

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Recently, novel biotechnologies to quantify RNA modifications became an increasingly popular choice for researchers who study epitranscriptome. When studying RNA methylations such as N6-methyladenosine (m6A), researchers need to make several decisions in its experimental design, especially the sample size and a proper statistical power. Due to the complexity and high-throughput nature of m6A sequencing measurements, methods for power calculation and study design are still currently unavailable. In this work, we propose a statistical power assessment tool, magpie, for power calculation and experimental design for epitranscriptome studies using m6A sequencing data. Our simulation-based power assessment tool will borrow information from real pilot data, and inspect various influential factors including sample size, sequencing depth, effect size, and basal expression ranges. We integrate two modules in magpie: (i) a flexible and realistic simulator module to synthesize m6A sequencing data based on real data; and (ii) a power assessment module to examine a set of comprehensive evaluation metrics.

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Schauerte, Maik, Nadiia Pozhydaieva, and Katharina Höfer. "Shaping the Bacterial Epitranscriptome—5′‐Terminal and Internal RNA Modifications." Advanced Biology 5, no. 8 (2021): 2100834. http://dx.doi.org/10.1002/adbi.202100834.

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Nossent, Anne Yaël. "The epitranscriptome: tools to study, manipulate, and exploit RNA modifications." Cardiovascular Research 115, no. 13 (2019): e133-e135. http://dx.doi.org/10.1093/cvr/cvz265.

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Xhemalçe, Blerta, Kyle M. Miller, and Natalia Gromak. "Epitranscriptome in action: RNA modifications in the DNA damage response." Molecular Cell 84, no. 19 (2024): 3610–26. http://dx.doi.org/10.1016/j.molcel.2024.09.003.

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Wei, Zhen, Subbarayalu Panneerdoss, Santosh Timilsina, et al. "Topological Characterization of Human and Mouse m5C Epitranscriptome Revealed by Bisulfite Sequencing." International Journal of Genomics 2018 (June 13, 2018): 1–19. http://dx.doi.org/10.1155/2018/1351964.

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Background. Compared with the well-studied 5-methylcytosine (m5C) in DNA, the role and topology of epitranscriptome m5C remain insufficiently characterized. Results. Through analyzing transcriptome-wide m5C distribution in human and mouse, we show that the m5C modification is significantly enriched at 5′ untranslated regions (5′UTRs) of mRNA in human and mouse. With a comparative analysis of the mRNA and DNA methylome, we demonstrate that, like DNA methylation, transcriptome m5C methylation exhibits a strong clustering effect. Surprisingly, an inverse correlation between mRNA and DNA m5C methylation is observed at CpG sites. Further analysis reveals that RNA m5C methylation level is positively correlated with both RNA expression and RNA half-life. We also observed that the methylation level of mitochondrial RNAs is significantly higher than RNAs transcribed from the nuclear genome. Conclusions. This study provides an in-depth topological characterization of transcriptome-wide m5C modification by associating RNA m5C methylation patterns with transcriptional expression, DNA methylations, RNA stabilities, and mitochondrial genome.

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García‑Vílchez, Raquel, Ana M. Añazco‑Guenkova, Sabine Dietmann, et al. "METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer." Molecular Cancer 22, no. 1 (2023): 119. https://doi.org/10.1186/s12943-023-01809-8.

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Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N7-methylguanosine (m7G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that <i>METTL1</i> depletion causes the loss of m7G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of <i>Mettl1</i> in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m7G tRNA methylation in cancer cell translation control and tumour biology.

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Taguchi, Y.-h. "Bioinformatic tools for epitranscriptomics." American Journal of Physiology-Cell Physiology, December 5, 2022. http://dx.doi.org/10.1152/ajpcell.00437.2022.

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The epitranscriptome, defined as RNA modifications that do not involve alterations in the nucleotide sequence, is a popular topic in the genomic sciences. Because we need massive computational techniques to identify epitranscriptomes within individual transcripts, many tools have been developed to infer epitranscriptomic sites as well as to process data sets using high-throughput sequencing. In this review, we have summarized recent developments in epitranscriptome spatial detection and data analysis and discussed their progression.

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Hashmi, Muhammad Abu Talha Safdar, Hooriya Fatima, Sadia Ahmad, Amna Rehman, and Fiza Safdar. "The interplay between epitranscriptomic RNA modifications and neurodegenerative disorders: Mechanistic insights and potential therapeutic strategies." Ibrain, November 11, 2024. http://dx.doi.org/10.1002/ibra.12183.

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AbstractNeurodegenerative disorders encompass a group of age‐related conditions characterized by the gradual decline in both the structure and functionality of the central nervous system (CNS). RNA modifications, arising from the epitranscriptome or RNA‐modifying protein mutations, have recently been observed to contribute significantly to neurodegenerative disorders. Specific modifications like N6‐methyladenine (m6A), N1‐methyladenine (m1A), 5‐methylcytosine (m5C), pseudouridine and adenosine‐to‐inosine (A‐to‐I) play key roles, with their regulators serving as crucial therapeutic targets. These epitranscriptomic changes intricately control gene expression, influencing cellular functions and contributing to disease pathology. Dysregulation of RNA metabolism, affecting mRNA processing and noncoding RNA biogenesis, is a central factor in these diseases. This review underscores the complex relationship between RNA modifications and neurodegenerative disorders, emphasizing the influence of RNA modification and the epitranscriptome, exploring the function of RNA modification enzymes in neurodegenerative processes, investigating the functional consequences of RNA modifications within neurodegenerative pathways, and evaluating the potential therapeutic advancements derived from assessing the epitranscriptome.

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Jousma, Jordan, Zhenbo Han, Gege Yan, et al. "Alteration of the N⁶-methyladenosine epitranscriptomic profile in synthetic phthalate-treated human induced pluripotent stem cell-derived endothelial cells." Epigenomics, October 31, 2022. http://dx.doi.org/10.2217/epi-2022-0110.

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Background: This study aimed to characterize the N6-methyladenosine epitranscriptomic profile induced by mono(2-ethylhexyl) phthalate (MEHP) exposure using a human-induced pluripotent stem cell-derived endothelial cell model. Methods: A multiomic approach was employed by performing RNA sequencing in parallel with an N6-methyladenosine-specific microarray to identify mRNAs, lncRNAs, and miRNAs affected by MEHP exposure. Results: An integrative multiomic analysis identified relevant biological features affected by MEHP, while functional assays provided a phenotypic characterization of these effects. Transcripts regulated by the epitranscriptome were validated with quantitative PCR and methylated RNA immunoprecipitation. Conclusion: The authors' profiling of the epitranscriptome expands the scope of toxicological insights into known environmental toxins to under surveyed cellular contexts and emerging domains of regulation and is, therefore, a valuable resource to human health.

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Journal articles on the topic 'RNA epitranscriptome'

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