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Artykuły w czasopismach na temat „Non-canonical initiation codon”

Autor: Grafiati

Data publikacji: 14 września 2024

Data aktualizacji: 31 lipca 2025

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1

Firth, Andrew E., and Ian Brierley. "Non-canonical translation in RNA viruses." Journal of General Virology 93, no. 7 (2012): 1385–409. http://dx.doi.org/10.1099/vir.0.042499-0.

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Viral protein synthesis is completely dependent upon the translational machinery of the host cell. However, many RNA virus transcripts have marked structural differences from cellular mRNAs that preclude canonical translation initiation, such as the absence of a 5′ cap structure or the presence of highly structured 5′UTRs containing replication and/or packaging signals. Furthermore, whilst the great majority of cellular mRNAs are apparently monocistronic, RNA viruses must often express multiple proteins from their mRNAs. In addition, RNA viruses have very compact genomes and are under intense

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Prasad, Sharanya, Shelley Starck, and Nilabh Shastri. "Presentation of cryptic peptides by MHC I molecules is enhanced by inflammatory stimuli. (P5003)." Journal of Immunology 190, no. 1_Supplement (2013): 110.2. http://dx.doi.org/10.4049/jimmunol.190.supp.110.2.

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Abstract Cytolytic T cells eliminate infected cells by recognizing intracellular peptides presented by MHC class I molecules. The antigenic peptides are derived primarily from newly synthesized proteins including those produced by cryptic translation. Previous studies have shown that in addition to the canonical AUG codon, translation can be initiated at non-AUG codons . Furthermore, translation initiation at non-AUG codons such as CUG is mechanistically distinct from canonical translation initiation as it is resistant to protein synthesis inhibitors that cause global translation shutdown. Her

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3

Austin, Jermaine, Subin Myoong, Natalia Badnarek, and Sridevi Challa. "Abstract 1407: Alterations of EIF1AX and carboplatin treatment induce non-canonical translation initiation in ovarian cancer." Cancer Research 85, no. 8_Supplement_1 (2025): 1407. https://doi.org/10.1158/1538-7445.am2025-1407.

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Abstract Ovarian cancer (OvCa) is the deadliest gynecologic malignancy with high mortality due to chemoresistance. High grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. The standard of care for women with HGSOC is cytoreductive surgery and chemotherapy using carboplatin, which causes DNA damage and oxidative stress. Despite aggressive treatment strategies, most patients with high grade HGSOC relapse. We recently demonstrated that post-translational modification of ribosomal proteins affects mRNA translation and protein homeostasis in ovarian cancer cells by reg

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4

Coldwell, Mark J., Ulrike Sack, Joanne L. Cowan, et al. "Multiple isoforms of the translation initiation factor eIF4GII are generated via use of alternative promoters, splice sites and a non-canonical initiation codon." Biochemical Journal 448, no. 1 (2012): 1–11. http://dx.doi.org/10.1042/bj20111765.

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During the initiation stage of eukaryotic mRNA translation, the eIF4G (eukaryotic initiation factor 4G) proteins act as an aggregation point for recruiting the small ribosomal subunit to an mRNA. We previously used RNAi (RNA interference) to reduce expression of endogenous eIF4GI proteins, resulting in reduced protein synthesis rates and alterations in the morphology of cells. Expression of EIF4G1 cDNAs, encoding different isoforms (f–a) which arise through selection of alternative initiation codons, rescued translation to different extents. Furthermore, overexpression of the eIF4GII paralogue

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5

Graça, Rafael, Rafael Fernandes, Ana Catarina Alves, Juliane Menezes, Luísa Romão, and Mafalda Bourbon. "Characterization of Two Variants at Met 1 of the Human LDLR Gene Encoding the Same Amino Acid but Causing Different Functional Phenotypes." Biomedicines 9, no. 9 (2021): 1219. http://dx.doi.org/10.3390/biomedicines9091219.

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Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism, characterized by increased levels of total and LDL plasma cholesterol, which leads to premature atherosclerosis and coronary heart disease. FH phenotype has considerable genetic heterogeneity and phenotypic variability, depending on LDL receptor activity and lifestyle. To improve diagnosis and patient management, here, we characterized two single nucleotide missense substitutions at Methionine 1 of the human LDLR gene (c.1A>T/p.(Met1Leu) and c.1A>C/p.(Met1Leu)). We used a combination of Western bl

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6

Gao, Fei, Maria Wesolowska, Reuven Agami, et al. "Using mitoribosomal profiling to investigate human mitochondrial translation." Wellcome Open Research 2 (December 11, 2017): 116. http://dx.doi.org/10.12688/wellcomeopenres.13119.1.

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Background: Gene expression in human mitochondria has various idiosyncratic features. One of these was recently revealed as the unprecedented recruitment of a mitochondrially-encoded tRNA as a structural component of the large mitoribosomal subunit. In porcine particles this is mt-tRNAPhe whilst in humans it is mt-tRNAVal. We have previously shown that when a mutation in mt-tRNAVal causes very low steady state levels, there is preferential recruitment of mt-tRNAPhe. We have investigated whether this altered mitoribosome affects intra-organellar protein synthesis. Methods: By using mitoribosoma

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7

Gao, Fei, Maria Wesolowska, Reuven Agami, et al. "Using mitoribosomal profiling to investigate human mitochondrial translation." Wellcome Open Research 2 (January 29, 2018): 116. http://dx.doi.org/10.12688/wellcomeopenres.13119.2.

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Background: Gene expression in human mitochondria has various idiosyncratic features. One of these was recently revealed as the unprecedented recruitment of a mitochondrially-encoded tRNA as a structural component of the large mitoribosomal subunit. In porcine particles this is mt-tRNAPhe whilst in humans it is mt-tRNAVal. We have previously shown that when a mutation in mt-tRNAVal causes very low steady state levels, there is preferential recruitment of mt-tRNAPhe. We have investigated whether this altered mitoribosome affects intra-organellar protein synthesis. Methods: By using mitoribosoma

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8

Fecher-Trost, Claudia, Ulrich Wissenbach, Andreas Beck, et al. "The in Vivo TRPV6 Protein Starts at a Non-AUG Triplet, Decoded as Methionine, Upstream of Canonical Initiation at AUG." Journal of Biological Chemistry 288, no. 23 (2013): 16629–44. http://dx.doi.org/10.1074/jbc.m113.469726.

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TRPV6 channels function as epithelial Ca2+ entry pathways in the epididymis, prostate, and placenta. However, the identity of the endogenous TRPV6 protein relies on predicted gene coding regions and is only known to a certain level of approximation. We show that in vivo the TRPV6 protein has an extended N terminus. Translation initiates at a non-AUG codon, at ACG, which is decoded by methionine and which is upstream of the annotated AUG, which is not used for initiation. The in vitro properties of channels formed by the extended full-length TRPV6 proteins and the so-far annotated and smaller T

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9

Jewett, Mollie W., Sunny Jain, Angelika K. Linowski, Amit Sarkar, and Patricia A. Rosa. "Molecular characterization of the Borrelia burgdorferi in vivo-essential protein PncA." Microbiology 157, no. 10 (2011): 2831–40. http://dx.doi.org/10.1099/mic.0.051706-0.

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The conversion of nicotinamide to nicotinic acid by nicotinamidase enzymes is a critical step in maintaining NAD+ homeostasis and contributes to numerous important biological processes in diverse organisms. In Borrelia burgdorferi, the nicotinamidase enzyme, PncA, is required for spirochaete survival throughout the infectious cycle. Mammals lack nicotinamidases and therefore PncA may serve as a therapeutic target for Lyme disease. Contrary to the in vivo importance of PncA, the current annotation for the pncA ORF suggests that the encoded protein may be inactive due to the absence of an N-term

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10

Paudel, Dinesh Babu, and Hélène Sanfaçon. "Mapping of sequences in the 5’ region and 3’ UTR of tomato ringspot virus RNA2 that facilitate cap-independent translation of reporter transcripts in vitro." PLOS ONE 16, no. 4 (2021): e0249928. http://dx.doi.org/10.1371/journal.pone.0249928.

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Tomato ringspot virus (ToRSV, genus Nepovirus, family Secoviridae, order Picornavirales) is a bipartite positive-strand RNA virus, with each RNA encoding one large polyprotein. ToRSV RNAs are linked to a 5’-viral genome-linked protein (VPg) and have a 3’ polyA tail, suggesting a non-canonical cap-independent translation initiation mechanism. The 3’ untranslated regions (UTRs) of RNA1 and RNA2 are unusually long (~1.5 kb) and share several large stretches of sequence identities. Several putative in-frame start codons are present in the 5’ regions of the viral RNAs, which are also highly conserv

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11

Alekhina, Olga, Ilya Terenin, Sergey Dmitriev, and Konstantin Vassilenko. "Functional Cyclization of Eukaryotic mRNAs." International Journal of Molecular Sciences 21, no. 5 (2020): 1677. http://dx.doi.org/10.3390/ijms21051677.

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The closed-loop model of eukaryotic translation states that mRNA is circularized by a chain of the cap-eIF4E-eIF4G-poly(A)-binding protein (PABP)-poly(A) interactions that brings 5′ and 3′ ends together. This circularization is thought to promote the engagement of terminating ribosomes to a new round of translation at the same mRNA molecule, thus enhancing protein synthesis. Despite the general acceptance and the elegance of the hypothesis, it has never been proved experimentally. Using continuous in situ monitoring of luciferase synthesis in a mammalian in vitro system, we show here that the

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12

Rahman, M. Sayeedur, Jason A. Simser, Kevin R. Macaluso, and Abdu F. Azad. "Functional analysis of secA homologues from rickettsiae." Microbiology 151, no. 2 (2005): 589–96. http://dx.doi.org/10.1099/mic.0.27556-0.

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The molecular basis of protein secretion that underlines rickettsial pathogenesis remains unknown. This paper reports the molecular and functional analysis of the putative secA gene, an essential component of the Sec-dependent protein secretion pathway, from Rickettsia rickettsii and Rickettsia typhi, the aetiological agents of Rocky Mountain spotted fever and murine typhus, respectively. The sequence analysis of the cloned secA genes from R. rickettsii and R. typhi show ORFs of 2721 and 2718 nt, respectively. Alignment of the deduced amino acid sequences reveals the presence of highly conserv

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13

Truniger, Verónica, Giuliano Sting Pechar, and Miguel A. Aranda. "Advances in Understanding the Mechanism of Cap-Independent Cucurbit Aphid-Borne Yellows Virus Protein Synthesis." International Journal of Molecular Sciences 24, no. 24 (2023): 17598. http://dx.doi.org/10.3390/ijms242417598.

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Non-canonical translation mechanisms have been described for many viral RNAs. In the case of several plant viruses, their protein synthesis is controlled by RNA elements in their genomic 3′-ends that are able to enhance cap-independent translation (3′-CITE). The proposed general mechanism of 3′-CITEs includes their binding to eukaryotic translation initiation factors (eIFs) that reach the 5′-end and AUG start codon through 5′-3′-UTR-interactions. It was previously shown that cucurbit aphid-borne yellows virus (CABYV) has a 3′-CITE, which varies in sequence and structure depending on the phylog

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14

Wu, Yu, Jianling Xie, Xin Jin, et al. "eEF2K enhances expression of PD-L1 by promoting the translation of its mRNA." Biochemical Journal 477, no. 22 (2020): 4367–81. http://dx.doi.org/10.1042/bcj20200697.

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Emerging advances in cancer therapy have transformed the landscape towards cancer immunotherapy regimens. Recent discoveries have resulted in the development of clinical immune checkpoint inhibitors that are ‘game-changers’ for cancer immunotherapy. Here we show that eEF2K, an atypical protein kinase that negatively modulates the elongation stage of protein synthesis, promotes the synthesis of PD-L1, an immune checkpoint protein which helps cancer cells to escape from immunosurveillance. Ablation of eEF2K in prostate and lung cancer cells markedly reduced the expression levels of the PD-L1 pro

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15

Starck, Shelley R., Vivian Jiang, Mariana Pavon-Eternod, et al. "Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I." Science 336, no. 6089 (2012): 1719–23. http://dx.doi.org/10.1126/science.1220270.

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Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non–AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons. CUG/Leu-tRNA initiation was independent of t

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16

Pan, Bingchen, Bowen Zheng, Chengzhong Xing, and Jingwei Liu. "Non-Canonical Programmed Cell Death in Colon Cancer." Cancers 14, no. 14 (2022): 3309. http://dx.doi.org/10.3390/cancers14143309.

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Programmed cell death (PCD) is an evolutionarily conserved process of cell suicide that is regulated by various genes and the interaction of multiple signal pathways. Non-canonical programmed cell death (PCD) represents different signaling excluding apoptosis. Colon cancer is the third most incident and the fourth most mortal worldwide. Multiple factors such as alcohol, obesity, and genetic and epigenetic alternations contribute to the carcinogenesis of colon cancer. In recent years, emerging evidence has suggested that diverse types of non-canonical programmed cell death are involved in the i

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17

Meinnel, T., C. Sacerdot, M. Graffe, S. Blanquet, and M. Springer. "Discrimination by Escherichia coli initiation factor IF3 against initiation on non-canonical codons relies on complementarity rules." Journal of Molecular Biology 290, no. 4 (1999): 825–37. http://dx.doi.org/10.1006/jmbi.1999.2881.

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Castelli, Lydia M., Wan-Ping Huang, Ya-Hui Lin, Kung-Yao Chang, and Guillaume M. Hautbergue. "Mechanisms of repeat-associated non-AUG translation in neurological microsatellite expansion disorders." Biochemical Society Transactions 49, no. 2 (2021): 775–92. http://dx.doi.org/10.1042/bst20200690.

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Repeat-associated non-AUG (RAN) translation was discovered in 2011 in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1). This non-canonical form of translation occurs in all reading frames from both coding and non-coding regions of sense and antisense transcripts carrying expansions of trinucleotide to hexanucleotide repeat sequences. RAN translation has since been reported in 7 of the 53 known microsatellite expansion disorders which mainly present with neurodegenerative features. RAN translation leads to the biosynthesis of low-complexity polymeric repeat proteins with

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19

Monteuuis, Geoffray, Anna Miścicka, Michał Świrski, et al. "Non-canonical translation initiation in yeast generates a cryptic pool of mitochondrial proteins." Nucleic Acids Research 47, no. 11 (2019): 5777–91. http://dx.doi.org/10.1093/nar/gkz301.

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Abstract Utilization of non-AUG alternative translation start sites is most common in bacteria and viruses, but it has been also reported in other organisms. This phenomenon increases proteome complexity by allowing expression of multiple protein isoforms from a single gene. In Saccharomyces cerevisiae, a few described cases concern proteins that are translated from upstream near-cognate start codons as N-terminally extended variants that localize to mitochondria. Using bioinformatics tools, we provide compelling evidence that in yeast the potential for producing alternative protein isoforms b

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Baudet, Mathieu, Philippe Ortet, Jean-Charles Gaillard, et al. "Proteomics-based Refinement ofDeinococcus desertiGenome Annotation Reveals an Unwonted Use of Non-canonical Translation Initiation Codons." Molecular & Cellular Proteomics 9, no. 2 (2009): 415–26. http://dx.doi.org/10.1074/mcp.m900359-mcp200.

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Schmitz, J. "Non-canonical translation mechanisms in plants: efficient in vitro and in planta initiation at AUU codons of the tobacco mosaic virus enhancer sequence." Nucleic Acids Research 24, no. 2 (1996): 257–63. http://dx.doi.org/10.1093/nar/24.2.257.

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Sikandar, Shaheen, Diana Dizon, Xiling Shen, Zuomei Li, Jeffery Besterman, and Steven M. Lipkin. "The Class I Hdac Inhibitor Mgcd0103 Induces Cell Cycle Arrest and Apoptosis in Colon Cancer Initiating Cells by Upregulating Dickkopf-1 and Non-Canonical Wnt Signaling." Oncotarget 1, no. 7 (2010): 596–605. http://dx.doi.org/10.18632/oncotarget.194.

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Slack, Jeffrey, Christopher Nguyen, and Amanda Ibe-Enwo. "A Lac Repressor-Inducible Baculovirus Expression Vector for Controlling Adeno-Associated Virus Capsid Ratios." Viruses 16, no. 1 (2023): 51. http://dx.doi.org/10.3390/v16010051.

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The baculovirus expression vector (BEV) system is an efficient, cost-effective, and scalable method to produce recombinant adeno-associated virus (rAAV) gene therapy vectors. Most BEV designs emulate the wild-type AAV transcriptome and translate the AAV capsid proteins, VP1, VP2, and VP3, from a single mRNA transcript with three overlapping open reading frames (ORFs). Non-canonical translation initiation codons for VP1 and VP2 reduce their abundances relative to VP3. Changing capsid ratios to improve rAAV vector efficacy requires a theoretical modification of the translational context. We have

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Lin, Kangyu, and John Paul Shen. "Abstract 6066: Elucidating cancer stem cells heterogeneity in colorectal cancer by single-cell RNA sequencing." Cancer Research 82, no. 12_Supplement (2022): 6066. http://dx.doi.org/10.1158/1538-7445.am2022-6066.

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Abstract Cancer stem cells (CSCs) are a small subpopulation of cells with capabilities of self-renewal and differentiation potential and have been suggested to play a critical role in tumor-initiation, metastasis, and multidrug resistance. The marker genes used to identify CSCs in CRC and transcriptional state of these cell is not fully elucidated due to the plasticity and dynamic nature of CSCs. In this study, we perform single-cell RNA sequencing (scRNA-seq) on primary CRC and liver metastases from CRC to evaluate the CSC population. We profiled approximately 80,000 single cells from neoadju

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Jiang, Qingwen, Manisha Raghavan, Britney Forsyth, et al. "Abstract 2648: ZFP36L2 orchestrates stress adaptive plasticity during injury repair and metastasis." Cancer Research 85, no. 8_Supplement_1 (2025): 2648. https://doi.org/10.1158/1538-7445.am2025-2648.

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Abstract Phenotypic plasticity is emerging as a key hallmark of cancer progression, yet the molecular mechanisms of cancer cell reprogramming remain poorly understood. Using single cell RNA sequencing of synchronously surgically resected matched trios of normal colon, primary and metastatic tumors from colorectal cancer (CRC) patients, we recently demonstrated that CRC undergoes highly conserved sequential phenotypic transitions during tumor progression: (1) differentiated epithelial cells dedifferentiate into an LGR5+ intestinal stem cell (ISC) state during primary tumor initiation (2) dissem

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Price, Lauren E., Abigail B. Loewen Faul, Aleksandra Vuchkovska, et al. "Molecular Genetic Analysis of Rbm45/Drbp1: Genomic Structure, Expression, and Evolution." Journal of Student Research 7, no. 2 (2019): 49–61. http://dx.doi.org/10.47611/jsr.v7i2.426.

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RNA recognition motif-type RNA-binding domain containing proteins (RBDPs) participate in RNA metabolism including regulating mRNA stability, nuclear-cytoplasmic shuttling, and splicing. Rbm45 is an RBDP first cloned from rat brain and expressed spatiotemporally during rat neural development. More recently, RBM45 has been associated with pathological aggregates in the human neurological disorders amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer’s. Rbm45 and the neural developmental protein musashi-1 are in the same family of RDBPs and have similar expression patte

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Saks, Margaret E., John Oh, Austin C. Deets, George M. Mastorakos, and Susan Anne Martinis. "Translational Regulation of Gene Expression in Mycobacterium: A Means for Coordinating the Expression of Functionally Related Proteins." FASEB Journal 31, S1 (2017). http://dx.doi.org/10.1096/fasebj.31.1_supplement.759.7.

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Mycobacterium tuberculosis (Mtb) is one of the world's deadliest infectious agents. Consequently, a top priority has been to identify the mechanisms that Mtb uses to regulate the expression of genes involved in its virulence/persistence. Our over arching focus is on the translational regulation of gene expression. Our studies indicate that Mtb leverages differential codon usage and tRNA expression during both initiation and elongation to regulate protein synthesis.Translation initiation plays a key role in determining protein expression levels through its influence on the density of ribosomes

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Andreev, Dmitry E., Gary Loughran, Alla D. Fedorova, Maria S. Mikhaylova, Ivan N. Shatsky, and Pavel V. Baranov. "Non-AUG translation initiation in mammals." Genome Biology 23, no. 1 (2022). http://dx.doi.org/10.1186/s13059-022-02674-2.

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AbstractRecent proteogenomic studies revealed extensive translation outside of annotated protein coding regions, such as non-coding RNAs and untranslated regions of mRNAs. This non-canonical translation is largely due to start codon plurality within the same RNA. This plurality is often due to the failure of some scanning ribosomes to recognize potential start codons leading to initiation downstream—a process termed leaky scanning. Codons other than AUG (non-AUG) are particularly leaky due to their inefficiency. Here we discuss our current understanding of non-AUG initiation. We argue for a ne

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Song, Ziye, Youkyung Lim, Anneloes van Krimpen, et al. "CTG-initiated cryptic peptide translation up and downstream of a canonical ATG start codon is enhanced by TLR stimulation and induces tumor regression in mice." Cancer Immunology Research, June 3, 2025. https://doi.org/10.1158/2326-6066.cir-24-0467.

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Abstract Cytotoxic T-lymphocytes (CTLs) screen cells for signs of infection and transformation by recognizing peptides displayed on major histocompatibility complex (MHC) class I molecules. Next to canonical ATG-initiated open reading frames (ORFs), non-canonical translation can result in synthesis of non-conventional or `cryptic´ polypeptides. These can originate from translation initiation at non-canonical start codons, a process previously associated with inflammation and oncogenic transformation. Cryptic translation products are efficiently presented on MHC class I molecules and therefore

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Lee, Byeong Sung, Woon Jong Choi, Sang Woo Lee, Byoung Joon Ko, and Tae Hyeon Yoo. "Towards Engineering an Orthogonal Protein Translation Initiation System." Frontiers in Chemistry 9 (October 26, 2021). http://dx.doi.org/10.3389/fchem.2021.772648.

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In the last two decades, methods to incorporate non-canonical amino acids (ncAAs) into specific positions of a protein have advanced significantly; these methods have become general tools for engineering proteins. However, almost all these methods depend on the translation elongation process, and strategies leveraging the initiation process have rarely been reported. The incorporation of a ncAA specifically at the translation initiation site enables the installation of reactive groups for modification at the N-termini of proteins, which are attractive positions for introducing abiological grou

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Ayyub, Shreya Ahana, Divya Dobriyal, and Umesh Varshney. "Contributions of the N- and C-Terminal Domains of Initiation Factor 3 to Its Functions in the Fidelity of Initiation and Antiassociation of the Ribosomal Subunits." Journal of Bacteriology 199, no. 11 (2017). http://dx.doi.org/10.1128/jb.00051-17.

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ABSTRACT Initiation factor 3 (IF3) is one of the three conserved prokaryotic translation initiation factors essential for protein synthesis and cellular survival. Bacterial IF3 is composed of a conserved architecture of globular N- and C-terminal domains (NTD and CTD) joined by a linker region. IF3 is a ribosome antiassociation factor which also modulates selection of start codon and initiator tRNA. All the functions of IF3 have been attributed to its CTD by in vitro studies. However, the in vivo relevance of these findings has not been investigated. By generating complete and partial IF3 (inf

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Grove, Daisy J., Paul J. Russell, and Michael G. Kearse. "To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT‐1·DENR to deliver initiator tRNA to ribosomes." WIREs RNA 15, no. 2 (2024). http://dx.doi.org/10.1002/wrna.1833.

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AbstractSelection of the correct start codon is critical for high‐fidelity protein synthesis. In eukaryotes, this is typically governed by a multitude of initiation factors (eIFs), including eIF2·GTP that directly delivers the initiator tRNA (Met‐tRNAiMet) to the P site of the ribosome. However, numerous reports, some dating back to the early 1970s, have described other initiation factors having high affinity for the initiator tRNA and the ability of delivering it to the ribosome, which has provided a foundation for further work demonstrating non‐canonical initiation mechanisms using alternati

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Miścicka, Anna, Kristen Lu, Irina S. Abaeva, Tatyana V. Pestova, and Christopher U. T. Hellen. "Initiation of translation on nedicistrovirus and related intergenic region IRESs by their factor-independent binding to the P site of 80S ribosomes." RNA, April 11, 2023, rna.079599.123. http://dx.doi.org/10.1261/rna.079599.123.

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Initiation of translation on many viral mRNAs occurs by non-canonical mechanisms that involve 5’ end-independent binding of ribosomes to an internal ribosome entry site (IRES). The ~190 nt-long intergenic region (IGR) IRES of dicistroviruses such as Cricket paralysis virus (CrPV) initiates translation without Met-tRNAiMetor initiation factors. Advances in metagenomics have revealed numerous dicistrovirus-like genomes with shorter, structurally distinct IGRs, such as Nedicistrovirus (NediV) and Antarctic picorna-like virus 1 (APLV1). Like canonical IGR IRESs, the ~165 nt-long NediV-like IGRs co

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Sonobe, Yoshifumi, Jihad Aburas, Gopinath Krishnan, et al. "A C. elegans model of C9orf72-associated ALS/FTD uncovers a conserved role for eIF2D in RAN translation." Nature Communications 12, no. 1 (2021). http://dx.doi.org/10.1038/s41467-021-26303-x.

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AbstractA hexanucleotide repeat expansion GGGGCC in the non-coding region of C9orf72 is the most common cause of inherited amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toxic dipeptide repeats (DPRs) are synthesized from GGGGCC via repeat-associated non-AUG (RAN) translation. Here, we develop C. elegans models that express, either ubiquitously or exclusively in neurons, 75 GGGGCC repeats flanked by intronic C9orf72 sequence. The worms generate DPRs (poly-glycine-alanine [poly-GA], poly-glycine-proline [poly-GP]) and poly-glycine-arginine [poly-GR]), display neurodegene

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Huntzinger, Eric, Jordan Sinteff, Bastien Morlet, and Bertrand Séraphin. "HELZ2: a new, interferon-regulated, human 3′-5′ exoribonuclease of the RNB family is expressed from a non-canonical initiation codon." Nucleic Acids Research, August 21, 2023. http://dx.doi.org/10.1093/nar/gkad673.

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Abstract Proteins containing a RNB domain, originally identified in Escherichia coli RNase II, are widely present throughout the tree of life. Many RNB proteins have 3′-5′ exoribonucleolytic activity but some have lost catalytic activity during evolution. Database searches identified a new RNB domain-containing protein in human: HELZ2. Analysis of genomic and expression data combined with evolutionary information suggested that the human HELZ2 protein is produced from an unforeseen non-canonical initiation codon in Hominidae. This unusual property was confirmed experimentally, extending the hu

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Alghoul, Fatima, Schaeffer Laure, Gilbert Eriani, and Franck Martin. "Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition." eLife 10 (June 2, 2021). http://dx.doi.org/10.7554/elife.66369.

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During embryogenesis, Hox mRNA translation is tightly regulated by a sophisticated molecular mechanism that combines two RNA regulons located in their 5’UTR. First, an internal ribosome entry site (IRES) enables cap-independent translation. The second regulon is a translation inhibitory element or TIE, which ensures concomitant cap-dependent translation inhibition. In this study, we deciphered the molecular mechanisms of mouse Hoxa3 and Hoxa11 TIEs. Both TIEs possess an upstream open reading frame (uORF) that is critical to inhibit cap-dependent translation. However, the molecular mechanisms u

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Zhang, Yanchao, Tom S. Bailey, Philip Hittmeyer, Ludwig J. Dubois, Jan Theys, and Philippe Lambin. "Multiplex genetic manipulations in Clostridium butyricum and Clostridium sporogenes to secrete recombinant antigen proteins for oral-spore vaccination." Microbial Cell Factories 23, no. 1 (2024). http://dx.doi.org/10.1186/s12934-024-02389-y.

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Abstract Background Clostridium spp. has demonstrated therapeutic potential in cancer treatment through intravenous or intratumoral administration. This approach has expanded to include non-pathogenic clostridia for the treatment of various diseases, underscoring the innovative concept of oral-spore vaccination using clostridia. Recent advancements in the field of synthetic biology have significantly enhanced the development of Clostridium-based bio-therapeutics. These advancements are particularly notable in the areas of efficient protein overexpression and secretion, which are crucial for th

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Singh, Jitendra, Rishi Kumar Mishra, Shreya Ahana Ayyub, Tanweer Hussain, and Umesh Varshney. "The initiation factor 3 (IF3) residues interacting with initiator tRNA elbow modulate the fidelity of translation initiation and growth fitness in Escherichia coli." Nucleic Acids Research, November 18, 2022. http://dx.doi.org/10.1093/nar/gkac1053.

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Abstract Initiation factor 3 (IF3) regulates the fidelity of bacterial translation initiation by debarring the use of non-canonical start codons or non-initiator tRNAs and prevents premature docking of the 50S ribosomal subunit to the 30S pre-initiation complex (PIC). The C-terminal domain (CTD) of IF3 can carry out most of the known functions of IF3 and sustain Escherichia coli growth. However, the roles of the N-terminal domain (NTD) have remained unclear. We hypothesized that the interaction between NTD and initiator tRNAfMet (i-tRNA) is essential to coordinate the movement of the two domai

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Sonobe, Yoshifumi, Soojin Lee, Gopinath Krishnan, et al. "Translation of dipeptide repeat proteins in C9ORF72 ALS/FTD through unique and redundant AUG initiation codons." eLife 12 (September 7, 2023). http://dx.doi.org/10.7554/elife.83189.

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A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A hallmark of ALS/FTD pathology is the presence of dipeptide repeat (DPR) proteins, produced from both sense GGGGCC (poly-GA, poly-GP, poly-GR) and antisense CCCCGG (poly-PR, poly-PG, poly-PA) transcripts. Translation of sense DPRs, such as poly-GA and poly-GR, depends on non-canonical (non-AUG) initiation codons. Here, we provide evidence for canonical AUG-dependent translation of two antisense DPRs, poly-PR and poly-PG. A single AUG is requir

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Lopez, Jose V., Stanley Cevario, and Stephen J. O'Brien. "Complete Nucleotide Sequences of the Domestic Cat (Felis catus) Mitochondrial Genome and a Transposed mtDNA Tandem Repeat (Numt) in the Nuclear Genome." April 1, 1996. https://doi.org/10.1006/geno.1996.0188.

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The complete 17,009-bp mitochondrial genome of the domestic cat,Felis catus,has been sequenced and conforms largely to the typical organization of previously characterized mammalian mtDNAs. Codon usage and base composition also followed canonical vertebrate patterns, except for an unusual ATC (non-AUG) codon initiating the NADH dehydrogenase subunit 2 (ND2) gene. Two distinct repetitive motifs at opposite ends of the control region contribute to the relatively large size (1559 bp) of this carnivore mtDNA. Alignment of the feline mtDNA genome to a homologous 7946-bp nuclear mtDNA tandem repeat

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Meguerditchian, Caroline, David Baux, Thomas E. Ludwig, Emmanuelle Genin, David-Alexandre Trégouët, and Omar Soukarieh. "Enhancing the annotation of small ORF-altering variants using MORFEE: introducing MORFEEdb, a comprehensive catalog of SNVs affecting upstream ORFs in human 5′UTRs." NAR Genomics and Bioinformatics 7, no. 1 (2025). https://doi.org/10.1093/nargab/lqaf017.

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Abstract Non-canonical small open reading frames (sORFs) are among the main regulators of gene expression. The most studied of these are upstream ORFs (upORFs) located in the 5′-untranslated region (UTR) of coding genes. Internal ORFs (intORFs) in the coding sequence and downstream ORFs (dORFs) in the 3′UTR have received less attention. Different bioinformatics tools permit the prediction of single nucleotide variants (SNVs) altering upORFs, mainly those creating AUGs or deleting stop codons, but no tool predicts variants altering non-canonical translation initiation sites and those altering i

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Kienzle, Laura, Stefano Bettinazzi, Thierry Choquette, et al. "A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics." BMC Biology 21, no. 1 (2023). http://dx.doi.org/10.1186/s12915-023-01609-y.

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Abstract Background Mitochondria have a central role in cellular functions, aging, and in certain diseases. They possess their own genome, a vestige of their bacterial ancestor. Over the course of evolution, most of the genes of the ancestor have been lost or transferred to the nucleus. In humans, the mtDNA is a very small circular molecule with a functional repertoire limited to only 37 genes. Its extremely compact nature with genes arranged one after the other and separated by short non-coding regions suggests that there is little room for evolutionary novelties. This is radically different

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Rodriguez, Jose Manuel, Federico Abascal, Daniel Cerdán-Vélez, Laura Martínez Gómez, Jesús Vázquez, and Michael L. Tress. "Evidence for widespread translation of 5′ untranslated regions." Nucleic Acids Research, July 2, 2024. http://dx.doi.org/10.1093/nar/gkae571.

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Abstract Ribosome profiling experiments support the translation of a range of novel human open reading frames. By contrast, most peptides from large-scale proteomics experiments derive from just one source, 5′ untranslated regions. Across the human genome we find evidence for 192 translated upstream regions, most of which would produce protein isoforms with extended N-terminal ends. Almost all of these N-terminal extensions are from highly abundant genes, which suggests that the novel regions we detect are just the tip of the iceberg. These upstream regions have characteristics that are not ty

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sprotocols. "Quantitative Procedure to Analyze Nuclear β-Catenin Using Immunofluorescence Tissue Staining". 31 грудня 2014. https://doi.org/10.5281/zenodo.13655.

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Authors: Oriol Arqués, Irene Chicote, Stephan Tenbaum, Isabel Puig & Héctor G. Palmer ### Abstract The analysis of the amounts of several proteins, which are found in different sub-cellular compartments, by immunofluorescence can be affected by artifacts that need to be detected and, if possible, corrected. In the case of nuclear β-catenin, its detection is usually affected by the signal obtained from the plasma membrane of the cells (which contain the most abundant pool of the beta-catenin). Here we describe an improved method for relative quantification of nuclear β-catenin amounts in im

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