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1

Park, Joonhyeong, Se Hee Ahn, Myung Geun Shin, Hak Kyun Kim, and Suhwan Chang. "tRNA-Derived Small RNAs: Novel Epigenetic Regulators." Cancers 12, no. 10 (2020): 2773. http://dx.doi.org/10.3390/cancers12102773.

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An epigenetic change is a heritable genetic alteration that does not involve any nucleotide changes. While the methylation of specific DNA regions such as CpG islands or histone modifications, including acetylation or methylation, have been investigated in detail, the role of small RNAs in epigenetic regulation is largely unknown. Among the many types of small RNAs, tRNA-derived small RNAs (tsRNAs) represent a class of noncoding small RNAs with multiple roles in diverse physiological processes, including neovascularization, sperm maturation, immune modulation, and stress response. Regarding these roles, several pioneering studies have revealed that dysregulated tsRNAs are associated with human diseases, such as systemic lupus, neurological disorder, metabolic disorder, and cancer. Moreover, recent findings suggest that tsRNAs regulate the expression of critical genes linked with these diseases by a variety of mechanisms, including epigenetic regulation. In this review, we will describe different classes of tsRNAs based on their biogenesis and will focus on their role in epigenetic regulation.
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2

Xu, Wei-Lin, Ye Yang, Yi-Dan Wang, Liang-Hu Qu, and Ling-Ling Zheng. "Computational Approaches to tRNA-Derived Small RNAs." Non-Coding RNA 3, no. 1 (2017): 2. http://dx.doi.org/10.3390/ncrna3010002.

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3

Jia, Hongyuan, and Linling Zhang. "tRNA-derived small RNAs in disease immunity." Theranostics 15, no. 1 (2025): 245–57. https://doi.org/10.7150/thno.102650.

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4

Di Fazio, Arianna, Margarita Schlackow, Sheng Kai Pong, Adele Alagia, and Monika Gullerova. "Dicer dependent tRNA derived small RNAs promote nascent RNA silencing." Nucleic Acids Research 50, no. 3 (2022): 1734–52. http://dx.doi.org/10.1093/nar/gkac022.

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Abstract In mammalian cells, small non-coding RNAs (sncRNAs) negatively regulate gene expression in a pathway known as RNA interference (RNAi). RNAi can be categorized into post-transcriptional gene silencing (PTGS), which involves the cleavage of target messenger RNA (mRNA) or inhibition of translation in the cytoplasm, and transcriptional gene silencing (TGS), which is mediated by the establishment of repressive epigenetic marks at target loci. Transfer RNAs (tRNAs), which are essential for translation, can be processed into small ncRNAs, termed tRNA-derived small RNAs (tsRNAs). The biogenesis of tsRNAs and their role in gene expression regulation has not yet been fully understood. Here, we show that Dicer dependent tsRNAs promote gene silencing through a mechanism distinct from PTGS and TGS. tsRNAs can lead to downregulation of target genes by targeting introns via nascent RNA silencing (NRS) in nuclei. Furthermore, we show that Ago2 slicer activity is required for this mechanism. Synthetic tsRNAs can significantly reduce expression of a target gene at both RNA and protein levels. Target genes regulated by NRS are associated with various diseases, which further underpins its biological significance. Finally, we show that NRS is evolutionarily conserved and has the potential to be explored as a novel synthetic sRNA based therapeutic.
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5

Martinez, German, Sarah G. Choudury, and R. Keith Slotkin. "tRNA-derived small RNAs target transposable element transcripts." Nucleic Acids Research 45, no. 9 (2017): 5142–52. http://dx.doi.org/10.1093/nar/gkx103.

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6

Schorn, Andrea J., Michael J. Gutbrod, Chantal LeBlanc, and Rob Martienssen. "LTR-Retrotransposon Control by tRNA-Derived Small RNAs." Cell 170, no. 1 (2017): 61–71. http://dx.doi.org/10.1016/j.cell.2017.06.013.

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7

Garcia-Silva, Maria R., Florencia Cabrera-Cabrera, Roberta Ferreira Cura das Neves, Thaís Souto-Padrón, Wanderley de Souza, and Alfonso Cayota. "Gene Expression Changes Induced byTrypanosoma cruziShed Microvesicles in Mammalian Host Cells: Relevance of tRNA-Derived Halves." BioMed Research International 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/305239.

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At present, noncoding small RNAs are recognized as key players in novel forms of posttranscriptional gene regulation in most eukaryotes. However, canonical small RNA pathways seem to be lost or excessively simplified in some unicellular organisms includingTrypanosoma cruziwhich lack functional RNAi pathways. Recently, we reported the presence of alternate small RNA pathways inT. cruzimainly represented by homogeneous populations of tRNA- and rRNA-derived small RNAs, which are secreted to the extracellular medium included in extracellular vesicles. Extracellular vesicle cargo could be delivered to other parasites and to mammalian susceptible cells promoting metacyclogenesis and conferring susceptibility to infection, respectively. Here we analyzed the changes in gene expression of host HeLa cells induced by extracellular vesicles fromT. cruzi. As assessed by microarray assays a large set of genes in HeLa cells were differentially expressed upon incorporation ofT. cruzi-derived extracellular vesicles. The elicited response modified mainly host cell cytoskeleton, extracellular matrix, and immune responses pathways. Some genes were also modified by the most abundant tRNA-derived small RNAs included in extracellular vesicles. These data suggest that microvesicles secreted byT. cruzicould be relevant players in early events of theT. cruzihost cell interplay.
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8

Wang, Mengjun, Junfeng Guo, Wei Chen, Hong Wang, and Xiaotong Hou. "Emerging roles of tRNA-derived small RNAs in injuries." PeerJ 12 (October 24, 2024): e18348. http://dx.doi.org/10.7717/peerj.18348.

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tRNA-derived small RNAs (tsRNAs) are a novel class of small noncoding RNAs, precisely cleaved from tRNA, functioning as regulatory molecules. The topic of tsRNAs in injuries has not been extensively discussed, and studies on tsRNAs are entering a new era. Here, we provide a fresh perspective on this topic. We systematically reviewed the classification, generation, and biological functions of tsRNAs in response to stress, as well as their potential as biomarkers and therapeutic targets in various injuries, including lung injury, liver injury, renal injury, cardiac injury, neuronal injury, vascular injury, skeletal muscle injury, and skin injury. We also provided a fresh perspective on the association between stress-induced tsRNAs and organ injury from a clinical perspective.
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9

Pereira, Marisa, Diana R. Ribeiro, Miguel M. Pinheiro, Margarida Ferreira, Stefanie Kellner, and Ana R. Soares. "m5U54 tRNA Hypomodification by Lack of TRMT2A Drives the Generation of tRNA-Derived Small RNAs." International Journal of Molecular Sciences 22, no. 6 (2021): 2941. http://dx.doi.org/10.3390/ijms22062941.

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Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification and tsRNA formation. More specifically, m5U54 hypomodification is followed by overexpression of the ribonuclease angiogenin (ANG) that cleaves tRNAs near the anticodon, resulting in accumulation of 5′tRNA-derived stress-induced RNAs (5′tiRNAs), namely 5′tiRNA-GlyGCC and 5′tiRNA-GluCTC, among others. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tiRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tiRNA formation in mammalian cells. These results establish a link between tRNA hypomethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.
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10

Oberbauer, Vera, and Matthias Schaefer. "tRNA-Derived Small RNAs: Biogenesis, Modification, Function and Potential Impact on Human Disease Development." Genes 9, no. 12 (2018): 607. http://dx.doi.org/10.3390/genes9120607.

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Transfer RNAs (tRNAs) are abundant small non-coding RNAs that are crucially important for decoding genetic information. Besides fulfilling canonical roles as adaptor molecules during protein synthesis, tRNAs are also the source of a heterogeneous class of small RNAs, tRNA-derived small RNAs (tsRNAs). Occurrence and the relatively high abundance of tsRNAs has been noted in many high-throughput sequencing data sets, leading to largely correlative assumptions about their potential as biologically active entities. tRNAs are also the most modified RNAs in any cell type. Mutations in tRNA biogenesis factors including tRNA modification enzymes correlate with a variety of human disease syndromes. However, whether it is the lack of tRNAs or the activity of functionally relevant tsRNAs that are causative for human disease development remains to be elucidated. Here, we review the current knowledge in regard to tsRNAs biogenesis, including the impact of RNA modifications on tRNA stability and discuss the existing experimental evidence in support for the seemingly large functional spectrum being proposed for tsRNAs. We also argue that improved methodology allowing exact quantification and specific manipulation of tsRNAs will be necessary before developing these small RNAs into diagnostic biomarkers and when aiming to harness them for therapeutic purposes.
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11

Chen, Qi, Xudong Zhang, Junchao Shi, Menghong Yan, and Tong Zhou. "Origins and evolving functionalities of tRNA-derived small RNAs." Trends in Biochemical Sciences 46, no. 10 (2021): 790–804. http://dx.doi.org/10.1016/j.tibs.2021.05.001.

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12

Zhu, Lei, Xuesha Liu, Wenchen Pu, and Yong Peng. "tRNA-derived small non-coding RNAs in human disease." Cancer Letters 419 (April 2018): 1–7. http://dx.doi.org/10.1016/j.canlet.2018.01.015.

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13

Guo, Jiaxu, Xinzhe Chen, Jiahao Ren, Yunhong Wang, Kun Wang, and Sumin Yang. "The Role of tRNA-Derived Small RNAs (tsRNAs) in Regulating Cell Death of Cardiovascular Diseases." Biology 14, no. 2 (2025): 218. https://doi.org/10.3390/biology14020218.

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Transfer RNA is a class of non-coding RNA that plays a role in amino acid translocation during protein synthesis. After specific modification, the cleaved fragment is called tRNA-derived small RNA. The advancement of bioinformatics technology has led to an increase in the visibility of small RNA derived from tRNA, and their functions in biological processes are being revealed. These include gene silencing, transcription and translation, epigenetics, and cell death. These properties have led to the implication of tsRNAs in various diseases. Although the current research mainly focuses on the role of tRNA-derived small RNA in cancer, there is mounting evidence that they are also strongly associated with cardiovascular disease, including cardiac hypertrophy, atrial fibrillation, heart failure, and myocarditis. Therefore, the regulatory role of tRNA-derived small RNA in cardiovascular disease will become an emerging therapeutic strategy. This review succinctly summarizes the characteristics, classification, and regulatory effect of tsRNA. By exploring the mechanism of tsRNA, it will provide a new tool for the diagnosis and prognosis of cardiovascular disease.
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14

Li, Yun, Zongyu Yu, Wenlin Jiang, et al. "tRNA and tsRNA: From Heterogeneity to Multifaceted Regulators." Biomolecules 14, no. 10 (2024): 1340. http://dx.doi.org/10.3390/biom14101340.

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As the most ancient RNA, transfer RNAs (tRNAs) play a more complex role than their constitutive function as amino acid transporters in the protein synthesis process. The transcription and maturation of tRNA in cells are subject to stringent regulation, resulting in the formation of tissue- and cell-specific tRNA pools with variations in tRNA overall abundance, composition, modification, and charging levels. The heterogeneity of tRNA pools contributes to facilitating the formation of histocyte-specific protein expression patterns and is involved in diverse biological processes. Moreover, tRNAs can be recognized by various RNase under physiological and pathological conditions to generate tRNA-derived small RNAs (tsRNAs) and serve as small regulatory RNAs in various biological processes. Here, we summarize these recent insights into the heterogeneity of tRNA and highlight the advances in the regulation of tRNA function and tsRNA biogenesis by tRNA modifications. We synthesize diverse mechanisms of tRNA and tsRNA in embryonic development, cell fate determination, and epigenetic inheritance regulation. We also discuss the potential clinical applications based on the new knowledge of tRNA and tsRNA as diagnostic and prognostic biomarkers and new therapeutic strategies for multiple diseases.
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15

Zacharjasz, Julian, Anna M. Mleczko, Paweł Bąkowski, Tomasz Piontek, and Kamilla Bąkowska-Żywicka. "Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments." International Journal of Molecular Sciences 22, no. 11 (2021): 5711. http://dx.doi.org/10.3390/ijms22115711.

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Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.
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16

Xiong, Qunli, Yaguang Zhang, Junjun Li, and Qing Zhu. "Small Non-Coding RNAs in Human Cancer." Genes 13, no. 11 (2022): 2072. http://dx.doi.org/10.3390/genes13112072.

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Small non-coding RNAs are widespread in the biological world and have been extensively explored over the past decades. Their fundamental roles in human health and disease are increasingly appreciated. Furthermore, a growing number of studies have investigated the functions of small non-coding RNAs in cancer initiation and progression. In this review, we provide an overview of the biogenesis of small non-coding RNAs with a focus on microRNAs, PIWI-interacting RNAs, and a new class of tRNA-derived small RNAs. We discuss their biological functions in human cancer and highlight their clinical application as molecular biomarkers or therapeutic targets.
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17

Peng, Ruofan, Herbert J. Santos, and Tomoyoshi Nozaki. "Transfer RNA-Derived Small RNAs in the Pathogenesis of Parasitic Protozoa." Genes 13, no. 2 (2022): 286. http://dx.doi.org/10.3390/genes13020286.

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Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are newly identified non-coding small RNAs that have recently attracted attention due to their functional significance in both prokaryotes and eukaryotes. tsRNAs originated from the cleavage of precursor or mature tRNAs by specific nucleases. According to the start and end sites, tsRNAs can be broadly divided into tRNA halves (31–40 nucleotides) and tRNA-derived fragments (tRFs, 14–30 nucleotides). tsRNAs have been reported in multiple organisms to be involved in gene expression regulation, protein synthesis, and signal transduction. As a novel regulator, tsRNAs have also been identified in various protozoan parasites. The conserved biogenesis of tsRNAs in early-branching eukaryotes strongly suggests the universality of this machinery, which requires future research on their shared and potentially disparate biological functions. Here, we reviewed the recent studies of tsRNAs in several representative protozoan parasites including their biogenesis and the roles in parasite biology and intercellular communication. Furthermore, we discussed the remaining questions and potential future works for tsRNAs in this group of organisms.
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18

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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19

Li, Jian-Jun, Chuan Qin, Pei-Pei Xu, et al. "Pathological significance of tRNA-derived small RNAs in neurological disorders." Neural Regeneration Research 15, no. 2 (2020): 212. http://dx.doi.org/10.4103/1673-5374.265560.

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20

Drino, Aleksej, Vera Oberbauer, Conor Troger, et al. "Production and purification of endogenously modified tRNA-derived small RNAs." RNA Biology 17, no. 8 (2020): 1104–15. http://dx.doi.org/10.1080/15476286.2020.1733798.

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21

He, X., F. Li, B. Bor, et al. "Human tRNA-Derived Small RNAs Modulate Host–Oral Microbial Interactions." Journal of Dental Research 97, no. 11 (2018): 1236–43. http://dx.doi.org/10.1177/0022034518770605.

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Coevolution of the human host and its associated microbiota has led to sophisticated interactions to maintain a delicate homeostasis. Emerging evidence suggests that in addition to small molecules, peptides, and proteins, small regulatory noncoding RNAs (sRNAs) might play an important role in cross-domain interactions. In this study, we revealed the presence of diverse host transfer RNA–derived small RNAs (tsRNAs) among human salivary sRNAs. We selected 2 tsRNAs (tsRNA-000794 and tsRNA-020498) for further study based on their high sequence similarity to specific tRNAs from a group of Gram-negative oral bacteria, including Fusobacterium nucleatum, a key oral commensal and opportunistic pathogen. We showed that the presence of F. nucleatum triggers exosome-mediated release of tsRNA-000794 and tsRNA-020498 by human normal oral keratinocyte cells. Furthermore, both tsRNA candidates exerted a growth inhibition effect on F. nucleatum, likely through interference with bacterial protein biosynthesis, but did not affect the growth of Streptococcus mitis, a health-associated oral Gram-positive bacterium whose genome does not carry sequences bearing high similarity to either tsRNA. Our data provide the first line of evidence for the modulatory role of host-derived tsRNAs in the microbial-host interaction.
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22

Dhahbi, Joseph M., Stephen R. Spindler, Hani Atamna, Dario Boffelli, and David I. K. Martin. "Deep Sequencing of Serum Small RNAs Identifies Patterns of 5′ tRNA Half and YRNA Fragment Expression Associated with Breast Cancer." Biomarkers in Cancer 6 (January 2014): BIC.S20764. http://dx.doi.org/10.4137/bic.s20764.

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Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety of cellular functions. We have previously described tRNA- and YRNA-derived small RNAs circulating as components of larger complexes in the blood of humans and mice; the characteristics of these small RNAs imply specific processing, secretion, and physiological regulation. In this study, we have asked if changes in the serum abundance of these tRNA and YRNA fragments are associated with a diagnosis of cancer. We used deep sequencing and informatics analysis to catalog small RNAs in the sera of breast cancer cases and normal controls. 5′ tRNA halves and YRNA fragments are abundant in both groups, but we found that a breast cancer diagnosis is associated with changes in levels of specific subtypes. This prompted us to look at existing sequence datasets of serum small RNAs from 42 breast cancer cases, taken at the time of diagnosis. We find significant changes in the levels of specific 5′ tRNA halves and YRNA fragments associated with clinicopathologic characteristics of the cancer. Although these findings do not establish causality, they suggest that circulating 5′ tRNA halves and YRNA fragments with known cellular functions may participate in breast cancer syndromes and have potential as circulating biomarkers. Larger studies with multiple types of cancer are needed to adequately evaluate their potential use for the development of noninvasive cancer screening.
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23

Honda, Shozo, Phillipe Loher, Megumi Shigematsu, et al. "Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers." Proceedings of the National Academy of Sciences 112, no. 29 (2015): E3816—E3825. http://dx.doi.org/10.1073/pnas.1510077112.

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Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER− breast cancer, AR− prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated anticodon cleavage, which is promoted by sex hormones and their receptors. Resultant 5′- and 3′-SHOT-RNAs, corresponding to 5′- and 3′-tRNA halves, bear a cyclic phosphate (cP) and an amino acid at the 3′-end, respectively. By devising a “cP-RNA-seq” method that is able to exclusively amplify and sequence cP-containing RNAs, we identified the complete repertoire of 5′-SHOT-RNAs. Furthermore, 5′-SHOT-RNA, but not 3′-SHOT-RNA, has significant functional involvement in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis of hormone-dependent cancers and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets.
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24

Sarais, Fabio, Alvaro Perdomo-Sabogal, Klaus Wimmers, and Siriluck Ponsuksili. "tiRNAs: Insights into Their Biogenesis, Functions, and Future Applications in Livestock Research." Non-Coding RNA 8, no. 3 (2022): 37. http://dx.doi.org/10.3390/ncrna8030037.

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Transfer RNA (tRNA)-derived small RNAs (tsRNAs) belong to a group of transfer ribonucleic acid (tRNA)-derived fragments that have recently gained interest as molecules with specific biological functions. Their involvement in the regulation of physiological processes and pathological phenotypes suggests molecular roles similar to those of miRNAs. tsRNA biogenesis under specific physiological conditions will offer new perspectives in understanding diseases, and may provide new sources for biological marker design to determine and monitor the health status of farm animals. In this review, we focus on the latest discoveries about tsRNAs and give special attention to molecules initially thought to be mainly associated with tRNA-derived stress-induced RNAs (tiRNAs). We present an outline of their biological functions, offer a collection of useful databases, and discuss future research perspectives and applications in livestock basic and applied research.
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25

Garcia-Silva, Maria Rosa, Florencia Cabrera-Cabrera, Maria Catalina Güida, and Alfonso Cayota. "Hints of tRNA-Derived Small RNAs Role in RNA Silencing Mechanisms." Genes 3, no. 4 (2012): 603–14. http://dx.doi.org/10.3390/genes3040603.

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26

Hsieh, Li-Ching, Shu-I. Lin, Hui-Fen Kuo, and Tzyy-Jen Chiou. "Abundance of tRNA-derived small RNAs in phosphate-starved Arabidopsis roots." Plant Signaling & Behavior 5, no. 5 (2010): 537–39. http://dx.doi.org/10.4161/psb.11029.

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27

Lee, Yong Sun, Yoshiyuki Shibata, Ankit Malhotra, and Anindya Dutta. "A novel class of small RNAs: tRNA-derived RNA fragments (tRFs)." Genes & Development 23, no. 22 (2009): 2639–49. http://dx.doi.org/10.1101/gad.1837609.

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28

Ren, Bo, Xutong Wang, Jingbo Duan, and Jianxin Ma. "Rhizobial tRNA-derived small RNAs are signal molecules regulating plant nodulation." Science 365, no. 6456 (2019): 919–22. http://dx.doi.org/10.1126/science.aav8907.

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Rhizobial infection and root nodule formation in legumes require recognition of signal molecules produced by the bacteria and their hosts. Here, we show that rhizobial transfer RNA (tRNA)-derived small RNA fragments (tRFs) are signal molecules that modulate host nodulation. Three families of rhizobial tRFs were confirmed to regulate host genes associated with nodule initiation and development through hijacking the host RNA-interference machinery that involves ARGONAUTE 1. Silencing individual tRFs with the use of short tandem target mimics or by overexpressing their targets represses root hair curling and nodule formation, whereas repressing these targets with artificial microRNAs identical to the respective tRFs or mutating these targets with CRISPR-Cas9 promotes nodulation. Our findings thus uncover a bacterial small RNA–mediated mechanism for prokaryote-eukaryote interaction and may pave the way for enhancing nodulation efficiency in legumes.
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Martinez, German. "tRNA-derived small RNAs: New players in genome protection against retrotransposons." RNA Biology 15, no. 2 (2017): 170–75. http://dx.doi.org/10.1080/15476286.2017.1403000.

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30

Tian, Haihua, Zhenyu Hu, and Chuang Wang. "The Therapeutic Potential of tRNA-derived Small RNAs in Neurodegenerative Disorders." Aging and disease 13, no. 2 (2022): 389. http://dx.doi.org/10.14336/ad.2021.0903.

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31

Plawgo, Kinga, and Katarzyna Dorota Raczynska. "Context-Dependent Regulation of Gene Expression by Non-Canonical Small RNAs." Non-Coding RNA 8, no. 3 (2022): 29. http://dx.doi.org/10.3390/ncrna8030029.

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In recent functional genomics studies, a large number of non-coding RNAs have been identified. It has become increasingly apparent that noncoding RNAs are crucial players in a wide range of cellular and physiological functions. They have been shown to modulate gene expression on different levels, including transcription, post-transcriptional processing, and translation. This review aims to highlight the diverse mechanisms of the regulation of gene expression by small noncoding RNAs in different conditions and different types of human cells. For this purpose, various cellular functions of microRNAs (miRNAs), circular RNAs (circRNAs), snoRNA-derived small RNAs (sdRNAs) and tRNA-derived fragments (tRFs) will be exemplified, with particular emphasis on the diversity of their occurrence and on the effects on gene expression in different stress conditions and diseased cell types. The synthesis and effect on gene expression of these noncoding RNAs varies in different cell types and may depend on environmental conditions such as different stresses. Moreover, noncoding RNAs play important roles in many diseases, including cancer, neurodegenerative disorders, and viral infections.
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32

Sharma, Manu, and Upinder Singh. "Role of tRNA-Derived Fragments in Protozoan Parasite Biology." Cells 14, no. 2 (2025): 115. https://doi.org/10.3390/cells14020115.

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tRNA molecules are among the most fundamental and evolutionarily conserved RNA types, primarily facilitating the translation of genetic information from mRNA into proteins. Beyond their canonical role as adaptor molecules during protein synthesis, tRNAs have evolved to perform additional functions. One such non-canonical role for tRNAs is through the generation of tRNA-derived fragments via specific cleavage processes. These tRNA-derived small RNAs (tsRNAs) are present across all three domains of life, including in protozoan parasites. They are formed through the cleavage of the parent tRNA molecules at different sites, resulting in either tRNA halves or smaller fragments. The precise mechanisms underlying the synthesis of various tRNA-derived fragments, including the specific RNases involved, as well as their distinct functions and roles in parasite physiology, are not yet fully understood and remain an active area of ongoing research. However, their role in modulating gene expression, particularly during stress responses, is becoming increasingly evident. In this context, we discuss recent findings on the roles of tRNA-derived small RNA in various protozoan parasites. Furthermore, we investigate how these tsRNAs either modulate gene expression within the parasite itself or are packaged into extracellular vesicles to alter host gene expression, thereby promoting parasite survival and adaptation.
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Lee Marzano, Shin-Yi, Achal Neupane, and Leslie Domier. "Transcriptional and Small RNA Responses of the White Mold Fungus Sclerotinia sclerotiorum to Infection by a Virulence-Attenuating Hypovirus." Viruses 10, no. 12 (2018): 713. http://dx.doi.org/10.3390/v10120713.

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Mycoviruses belonging to the family Hypoviridae cause persistent infection of many different host fungi. We previously determined that the white mold fungus, Sclerotinia sclerotiorum, infected with Sclerotinia sclerotiorum hypovirus 2-L (SsHV2-L) exhibits reduced virulence, delayed/reduced sclerotial formation, and enhanced production of aerial mycelia. To gain better insight into the cellular basis for these changes, we characterized changes in mRNA and small RNA (sRNA) accumulation in S. sclerotiorum to infection by SsHV2-L. A total of 958 mRNAs and 835 sRNA-producing loci were altered after infection by SsHV2-L, among which &gt;100 mRNAs were predicted to encode proteins involved in the metabolism and trafficking of carbohydrates and lipids. Both S. sclerotiorum endogenous and virus-derived sRNAs were predominantly 22 nt in length suggesting one dicer-like enzyme cleaves both. Novel classes of endogenous small RNAs were predicted, including phasiRNAs and tRNA-derived small RNAs. Moreover, S. sclerotiorum phasiRNAs, which were derived from noncoding RNAs and have the potential to regulate mRNA abundance in trans, showed differential accumulation due to virus infection. tRNA fragments did not accumulate differentially after hypovirus infection. Hence, in-depth analysis showed that infection of S. sclerotiorum by a hypovirulence-inducing hypovirus produced selective, large-scale reprogramming of mRNA and sRNA production.
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34

Torres, Adrian Gabriel. "Enjoy the Silence: Nearly Half of Human tRNA Genes Are Silent." Bioinformatics and Biology Insights 13 (January 2019): 117793221986845. http://dx.doi.org/10.1177/1177932219868454.

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Transfer RNAs (tRNAs) are key components of the translation machinery. They read codons on messenger RNAs (mRNAs) and deliver the appropriate amino acid to the ribosome for protein synthesis. The human genome encodes more than 500 tRNA genes but their individual contribution to the cellular tRNA pool is unclear. In recent years, novel methods were developed to improve the quantification of tRNA gene expression, most of which rely on next-generation sequencing such as small RNA-Seq applied to tRNAs (tRNA-Seq). In a previous study, we presented a bioinformatics strategy to analyse tRNA-Seq datasets that we named ‘isodecoder-specific tRNA gene contribution profiling’ (Iso-tRNA-CP). Using Iso-tRNA-CP, we showed that tRNA gene expression is cell type- and tissue-specific and that this process can regulate tRNA-derived fragments abundance. An additional observation that stems from that work is that approximately half of human tRNA genes appeared silent or poorly expressed. In this commentary, I discuss this finding in light of the current literature and speculate on potential functions that transcriptionally silent tRNA genes may play. Studying silent tRNA genes may offer a unique opportunity to unravel novel mechanisms of cell regulation associated to tRNA biology.
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35

Haussecker, D., Y. Huang, A. Lau, P. Parameswaran, A. Z. Fire, and M. A. Kay. "Human tRNA-derived small RNAs in the global regulation of RNA silencing." RNA 16, no. 4 (2010): 673–95. http://dx.doi.org/10.1261/rna.2000810.

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36

Shen, Linyuan, Zhendong Tan, Mailin Gan, et al. "tRNA-Derived Small Non-Coding RNAs as Novel Epigenetic Molecules Regulating Adipogenesis." Biomolecules 9, no. 7 (2019): 274. http://dx.doi.org/10.3390/biom9070274.

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tRNA-derived fragments (tRFs), a novel type of non-coding RNA derived from tRNAs, play an important part in governing gene expressions at a post-transcriptional level. To date, the regulatory mechanism of tRFs governing fat deposition and adipogenesis is completely unknown. In this study, high fat diet was employed to induce an obese rat model, and tRFs transcriptome sequencing was conducted to identify differentially expressed tRFs that response to obesity. We found out that tRFGluTTC, which promoted preadipocyte proliferation by increasing expressions of cell cycle regulatory factors, had the highest fold change in the 296 differentially expressed tRFs. Moreover, tRFGluTTC also suppressed preadipocyte differentiation by reducing triglyceride content and lipid accumulation, and by decreasing expressions of genes that related to fatty acid synthesis. According to results of luciferase activity analysis, tRFGluTTC directly targeted Kruppel-like factor (KLF) 9, KLF11, and KLF12, thus significantly suppressing mRNA expressions of these target genes. Moreover, tRFGluTTC suppressed adipogenesis, accompanying by suppressing expressions of adipogenic transcription factors (aP2, PPARγ, and C/EBPα). In conclusion, these results imply that tRFGluTTC may act as a novel epigenetic molecule regulating adipogenesis and could provide a new strategy for the intervention treatment of obesity.
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37

Yang, Na, Ruijun Li, Ruai Liu, et al. "The Emerging Function and Promise of tRNA-Derived Small RNAs in Cancer." Journal of Cancer 15, no. 6 (2024): 1642–56. http://dx.doi.org/10.7150/jca.89219.

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38

Su, Zhangli, Briana Wilson, Pankaj Kumar, and Anindya Dutta. "Noncanonical Roles of tRNAs: tRNA Fragments and Beyond." Annual Review of Genetics 54, no. 1 (2020): 47–69. http://dx.doi.org/10.1146/annurev-genet-022620-101840.

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As one of the most abundant and conserved RNA species, transfer RNAs (tRNAs) are well known for their role in reading the codons on messenger RNAs and translating them into proteins. In this review, we discuss the noncanonical functions of tRNAs. These include tRNAs as precursors to novel small RNA molecules derived from tRNAs, also called tRNA-derived fragments, that are abundant across species and have diverse functions in different biological processes, including regulating protein translation, Argonaute-dependent gene silencing, and more. Furthermore, the role of tRNAs in biosynthesis and other regulatory pathways, including nutrient sensing, splicing, transcription, retroelement regulation, immune response, and apoptosis, is reviewed. Genome organization and sequence variation of tRNA genes are also discussed in light of their noncanonical functions. Lastly, we discuss the recent applications of tRNAs in genome editing and microbiome sequencing.
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39

Diebel, Kevin W., Kun Zhou, Aaron B. Clarke, and Lynne T. Bemis. "Beyond the Ribosome: Extra-translational Functions of tRNA Fragments." Biomarker Insights 11s1 (January 2016): BMI.S35904. http://dx.doi.org/10.4137/bmi.s35904.

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High-throughput sequencing studies of small RNAs reveal a complex milieu of noncoding RNAs in biological samples. Early data analysis was often limited to microRNAs due to their regulatory nature and potential as biomarkers; however, many more classes of noncoding RNAs are now being recognized. A class of fragments initially excluded from analysis were those derived from transfer RNAs (tRNAs) because they were thought to be degradation products. More recently, critical cellular function has been attributed to tRNA fragments (tRFs), and their conservation across all domains of life has propelled them into an emerging area of scientific study. The biogenesis of tRFs is currently being elucidated, and initial studies show that a diverse array of tRFs are genera ted from all parts of a tRNA molecule. The goal of this review was to present what is currently known about tRFs and their potential as biomarkers for the earlier detection of disease.
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40

Zhu, Qifan, Jane Allyn Kirby, Chen Chu, and Lan-Tao Gou. "Small Noncoding RNAs in Reproduction and Infertility." Biomedicines 9, no. 12 (2021): 1884. http://dx.doi.org/10.3390/biomedicines9121884.

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Infertility has been reported as one of the most common reproductive impairments, affecting nearly one in six couples worldwide. A large proportion of infertility cases are diagnosed as idiopathic, signifying a deficit in information surrounding the pathology of infertility and necessity of medical intervention such as assisted reproductive therapy. Small noncoding RNAs (sncRNAs) are well-established regulators of mammalian reproduction. Advanced technologies have revealed the dynamic expression and diverse functions of sncRNAs during mammalian germ cell development. Mounting evidence indicates sncRNAs in sperm, especially microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs), are sensitive to environmental changes and mediate the inheritance of paternally acquired metabolic and mental traits. Here, we review the critical roles of sncRNAs in mammalian germ cell development. Furthermore, we highlight the functions of sperm-borne sncRNAs in epigenetic inheritance. We also discuss evidence supporting sncRNAs as promising biomarkers for fertility and embryo quality in addition to the present limitations of using sncRNAs for infertility diagnosis and treatment.
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Yap, Yoon Sing, Pasquale Patrizio, Luisa Cimmino, Konstantinos Sdrimas, and Aristeidis G. Telonis. "The Small Non-Coding RNA Profile of Human and Mouse Sperm." Non-Coding RNA 11, no. 1 (2025): 15. https://doi.org/10.3390/ncrna11010015.

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Small non-coding RNAs constitute a dynamic epigenetic layer in mature spermatozoa that can exert transgenerational regulatory functions. Here, we review recent advances in the field of small RNAs in spermatozoa, how their profiles change in response to lifestyle or environmental factors, and their impact on offsprings’ physiology. The profile of these RNAs changes dramatically during spermatozoa maturation. The majority of intracellular small RNAs during early spermatogenesis are miRNAs and piRNAs, but, in mature spermatozoa, tRNA- and rRNA-derived fragments (tRFs and rRFs, respectively) are the predominant forms, primarily delivered from the epididymis via extracellular vesicles. Diet, exercise, and environmental exposures have a direct effect on small RNA levels in spermatozoa, and this differential abundance can reprogram the development of the embryo. Offsprings of fathers with different lifestyles can have different phenotypes, including altered metabolism or behavior. Therefore, small RNAs in spermatozoa are emerging as an important epigenetic layer in development and transgenerational inheritance.
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42

Liang, Yan, Ji Zhang, Wenxian Qiu, et al. "Dysregulation of tRNA-derived small RNAs and their potential roles in lupus nephritis." Lupus 30, no. 14 (2021): 2248–55. http://dx.doi.org/10.1177/09612033211061482.

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Objective Lupus nephritis (LN) is a major end-organ complication of systemic lupus erythematosus (SLE), and the molecular mechanism of LN is not completely clear. Accumulating pieces of evidence indicate the potential vital role of tRNA-derived small RNAs (tsRNAs) in human diseases. Current study aimed to investigate the potential roles of tsRNAs in LN. Methods We herein employed high‐throughput sequencing to screen the expression profiles of tsRNAs in renal tissues of the LN and control groups. To validate the sequencing data, we performed quantitative real-time PCR (qRT-PCR) analysis. Correlational analysis of verified tsRNAs expression and clinical indicators was conducted using linear regression. The potential target genes were also predicted. The biological functions of tsRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results Our findings revealed that the expression profiles of tsRNAs were significantly altered in the kidney tissues from LN patients compared with control. Overall, 160 tsRNAs were significantly dysregulated in the LN group, of which 79 were upregulated, whereas 81 were downregulated. Subsequent qRT-PCR results confirmed the different expression of candidate tsRNAs. Correlation analysis results found that expression of verified tsRNAs were correlated to clinical indicators. The target prediction results revealed that verified tsRNAs might act on 712 target genes. Further bioinformatics analysis uncovered tsRNAs might participate in the pathogenesis of LN through several associated pathways, including cell adhesion molecules, MAPK signaling pathway, PI3K-Akt signaling pathway and B cell receptor signaling pathway. Conclusion This study provides a novel insight for studying the mechanism of LN.
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43

George, Suja, Mohammed Rafi, Maitha Aldarmaki, Mohamed ElSiddig, Mariam Al Nuaimi, and Khaled M. A. Amiri. "tRNA derived small RNAs—Small players with big roles." Frontiers in Genetics 13 (September 19, 2022). http://dx.doi.org/10.3389/fgene.2022.997780.

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In the past 2 decades, small non-coding RNAs derived from tRNA (tsRNAs or tRNA derived fragments; tRFs) have emerged as new powerful players in the field of small RNA mediated regulation of gene expression, translation, and epigenetic control. tRFs have been identified from evolutionarily divergent organisms from Archaea, the higher plants, to humans. Recent studies have confirmed their roles in cancers and other metabolic disorders in humans and experimental models. They have been implicated in biotic and abiotic stress responses in plants as well. In this review, we summarize the current knowledge on tRFs including types of tRFs, their biogenesis, and mechanisms of action. The review also highlights recent studies involving differential expression profiling of tRFs and elucidation of specific functions of individual tRFs from various species. We also discuss potential considerations while designing experiments involving tRFs identification and characterization and list the available bioinformatics tools for this purpose.
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44

Chu, Xiaohua, Chenyang He, Bo Sang, et al. "Transfer RNAs-derived small RNAs and their application potential in multiple diseases." Frontiers in Cell and Developmental Biology 10 (August 22, 2022). http://dx.doi.org/10.3389/fcell.2022.954431.

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The role of tRNAs is best known as adapter components of translational machinery. According to the central dogma of molecular biology, DNA is transcribed to RNA and in turn is translated into proteins, in which tRNA outstands by its role of the cellular courier. Recent studies have led to the revision of the canonical function of transfer RNAs (tRNAs), which indicates that tRNAs also serve as a source for short non-coding RNAs called tRNA-derived small RNAs (tsRNAs). tsRNAs play key roles in cellular processes by modulating complicated regulatory networks beyond translation and are widely involved in multiple diseases. Herein, the biogenesis and classification of tsRNAs were firstly clarified. tsRNAs are generated from pre-tRNAs or mature tRNAs and are classified into tRNA-derived fragments (tRFs) and tRNA halves (tiRNA). The tRFs include five types according to the incision loci: tRF-1, tRF-2, tRF-3, tRF-5 and i-tRF which contain 3′ tiRNA and 5′ tiRNA. The functions of tsRNAs and their regulation mechanisms involved in disease processes are systematically summarized as well. The mechanisms can elaborate on the specific regulation of tsRNAs. In conclusion, the current research suggests that tsRNAs are promising targets for modulating pathological processes, such as breast cancer, ischemic stroke, respiratory syncytial virus, osteoporosis and so on, and maintain vital clinical implications in diagnosis and therapeutics of various diseases.
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45

Mao, Mingwen, Weina Chen, Xingbiao Huang, and Dong Ye. "Role of tRNA-derived small RNAs(tsRNAs) in the diagnosis and treatment of malignant tumours." Cell Communication and Signaling 21, no. 1 (2023). http://dx.doi.org/10.1186/s12964-023-01199-w.

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AbstractMalignant tumours area leading cause of death globally, accounting for approximately 13% of all deaths. A detailed understanding of the mechanism(s) of the occurrence and development of malignant tumours and identification of relevant therapeutic targets are therefore key to tumour treatment. tsRNAs(tRNA-derived small RNAs)—also known as TRFs (tRNA-derived fragments), tiRNAs (tRNA-derived stress-induced RNAs), tRNA halves, etc.—are a recently identified class of small noncoding RNAs that are generated from mature tRNA or tRNA precursors through cleavage by enzymes such as angiogenin, Dicer, RNase Z, and RNase P. Several studies have confirmed that dysregulation of tsRNAs is closely related to the tumorigenesis of breast cancer, nasopharyngeal cancer, lung cancer, and so on. Furthermore, research indicates that tsRNAs can be used as clinical diagnostic markers and therapeutic targets for cancer. In our review, we summarized the recent research progress on the role and clinical application of tsRNAs in tumorigenesis and progression.
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Pereira, Marisa, Ribeiro Diana R., Pinheiro Miguel M., Margarida Ferreira, Stefanie Kellner, and Ana R. Soares. "m5U54 tRNAHypomodification by Lack of TRMT2ADrivesthe Generation of tRNA-Derived Small RNAs." International Journal of Molecular Sciences 22, no. 6 (2021). https://doi.org/10.3390/ijms22062941.

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47

Wilson, Briana, and Anindya Dutta. "Function and Therapeutic Implications of tRNA Derived Small RNAs." Frontiers in Molecular Biosciences 9 (April 13, 2022). http://dx.doi.org/10.3389/fmolb.2022.888424.

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tRNA derived small RNAs are mainly composed of tRNA fragments (tRFs) and tRNA halves (tiRs). Several functions have been attributed to tRFs and tiRs since their initial characterizations, spanning all aspects of regulation of the Central Dogma: from nascent RNA silencing, to post-transcriptional gene silencing, and finally, to translational regulation. The length distribution, sequence diversity, and multifaceted functions of tRFs and tiRs positions them as attractive new models for small RNA therapeutics. In this review, we will discuss the principles of tRF biogenesis and function in order to highlight their therapeutic potential.
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48

Yoshimoto, Rei, Fumiko Ishida, Miyuki Yamaguchi, and Shigeyuki Tanaka. "The production and secretion of tRNA-derived RNA fragments in the corn smut fungus Ustilago maydis." Frontiers in Fungal Biology 3 (August 4, 2022). http://dx.doi.org/10.3389/ffunb.2022.958798.

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The biogenesis of small non-coding RNAs is a molecular event that contributes to cellular functions. The basidiomycete fungus Ustilago maydis is a biotrophic pathogen parasitizing maize. A hallmark of its genome structure is an absence of RNAi machinery including Dicer and Argonaute proteins, which are responsible for the production of small RNAs in other organisms. However, it remains unclear whether U. maydis produces small RNAs during fungal growth. Here we found that U. maydis cells accumulate approximately 20-30 nucleotides of small RNA fragments during growth in the axenic culture condition. The RNA-seq analysis of these fragments identified that these small RNAs are originated from tRNAs and 5.8S ribosomal RNA. Interestingly, majority of their sequences are generated from tRNAs responsible for asparagine, glutamine and glycine, suggesting a bias of origin. The cleavage of tRNAs mainly occurs at the position near anticodon-stem-loop. We generated the deletion mutants of two genes nuc1 and nuc2 encoding RNase T2, which is a candidate enzyme that cleaves tRNAs. The deletion mutants of two genes largely fail to accumulate tRNA-derived RNA fragments. Nuc1 and tRNA are co-localized at the tip of budding cells and tRNA fragment could be detected in culture supernatant. Our results suggest that specific tRNAs would be cleaved during secretory processes and tRNA fragments might have extracellular functions.
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49

Chen, Qi, and Tong Zhou. "Emerging functional principles of tRNA-derived small RNAs and other regulatory small RNAs." Journal of Biological Chemistry, September 2023, 105225. http://dx.doi.org/10.1016/j.jbc.2023.105225.

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50

Koenig, Lisa, Victoria Guggenberger, Kristeli Eleftheriou, et al. "Copy Number Determination of Sperm-Borne Small RNAs Implied in the Intergenerational Inheritance of Metabolic Syndromes." RNA, May 28, 2025, rna.080480.125. https://doi.org/10.1261/rna.080480.125.

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Mammalian spermatocytes harbour small RNAs that are mostly degradation products of abundant non-coding RNAs, including ribosomal RNA-derived small RNAs (rsRNAs) and tRNA-derived RNAs (tDRs). Notably, tDRs have been implicated in inheriting paternally acquired traits in rodents. Direct experimental proof for this notion comes from manipulating fertilized murine oocytes through microinjection of small RNA preparations, resulting in metabolic changes measurable in the offspring. How these paternally transmitted small RNAs could function mechanistically in the developing zygote remains to be understood. Since nothing is known about how many small RNAs are required for functional impact, we aimed to determine the copy numbers of specific small RNAs contained in a single spermatocyte. Using hybridization-based methods that avoid amplification-induced biases, we estimated average copy numbers for specific tDRs and rsRNAs per murine spermatocyte. While the measured numbers allow an approximation of how many rRNA- and tRNA-derived RNAs enter a murine oocyte during fertilization, the magnitude of these numbers underscores the need for remaining cautious when interpreting the effects of non-physiological copy numbers of small RNAs that were used to manipulate a biological system.
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