Advances in the Generation and Biological Function of tsRNAs

doi:10.3969/j.issn.1671-2587.2025.03.021

JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE ›› 2025, Vol. 27 ›› Issue (3): 412-422.DOI: 10.3969/j.issn.1671-2587.2025.03.021

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Advances in the Generation and Biological Function of tsRNAs

LIU Yue, LIU Yao, WAN Jiuchao, GUAN Shengwen, ZHAO Pan

Department of Hematology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000

Received:2024-12-20 Published:2025-06-23

Abstract

Abstract: With the development of high-throughput sequencing technology, the advancement of bioinformatics technology, transfer RNAderived small RNAshave received widespread attention as a novel type of non-coding small RNAs. Based on the differences in nuclease cleavage sites on tRNAs, tsRNAs can be classified into four major categories: tRNA-derived fragments, tRF-1, tRNA-derived stress-inducible small RNAs, other unclassified tsRNAs, each of which has a specific subcellular localization. Recent studies have revealed that tRNAs play important roles in embryonic development, cell fate, immune regulation, the development of many human diseases. Therefore, this paper systematically reviews the biological origin, classification of tsRNAs, the biological functions of tsRNAs, including gene expression regulation, translational regulation, epigenetic regulation, reverse transcriptional regulation, neonatal RNA silencing, explores the feasibility of tsRNAs as diagnostic markers, therapeutic targets for diseases

Key words: tsRNA, small non-coding RNA, tRF, tiRNA, biological function

CLC Number:

LIU Yue, LIU Yao, WAN Jiuchao, GUAN Shengwen, ZHAO Pan. Advances in the Generation and Biological Function of tsRNAs[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(3): 412-422.

References

[1] RODNINA M V,WINTERMEYER W.The ribosome as a molecular machine:the mechanism of tRNA-mRNA movement in translocation[J]. Biochem Soc Trans,2011, 39(2):658-662.
[2] ZONG T Y,YANG Y Y,ZHAO H,et al.tsRNAs:Novel small molecules from cell function and regulatory mechanism to therapeutic targets[J]. Cell Prolif,2021, 54(3):e12977.
[3] YANG J,QI M L,FEI X,et al.Hsa_circRNA_0088036 acts as a CeRNA to promote bladder cancer progression by sponging miR-140-3p[J]. Cell Death Dis,2022, 13(4):322.
[4] FERNÁNDEZ-PATO A,VIRSEDA-BERDICES A,RESINO S,et al. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality[J]. Emerg Microbes Infect,2022,11(1):676-688.
[5] XIE L Z,HUANG G S,GAO M J,et al.Identification of atrial fibrillation-related lncRNA based on bioinformatic analysis[J]. Dis Markers,2022,2022:8307975.
[6] XIONG Q L,ZHANG Y G,LI J J,et al.Small non-coding RNAs in human cancer[J]. Genes (Basel),2022,13(11): 2072.
[7] LAKSHMANAN V,SUJITH T N,BANSAL D,et al.Comprehensive annotation and characterization of planarian tRNA and tRNA-derived fragments (tRFs)[J].RNA,2021,27(4):477-495.
[8] WANG Z S,ZHOU H C,WEI C Y,et al.Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis[J]. Parasit Vectors,2021,14(1):87.
[9] DIALLO I,HO J,LAMBERT M,et al.A tRNA-derived fragment present in E. coli OMVs regulates host cell gene expression and proliferation[J]. PLoS Pathog,2022, 18(9):e1010827.
[10] SUN Z X,HU Y,ZHOU Y L,et al.tRNA-derived fragments from wheat are potentially involved in susceptibility to Fusarium head blight[J]. BMC Plant Biol,2022,22(1):3.
[11] YING S Y,LI P C,WANG J Q,et al.tRF-Gln-CTG-026 ameliorates liver injury by alleviating global protein synthesis[J]. Signal Transduct Target Ther,2023,8(1): 144.
[12] YU X C,XIE Y Y,ZHANG S S,et al.tRNA-derived fragments:Mechanisms underlying their regulation of gene expression and potential applications as therapeutic targets in cancers and virus infections[J]. Theranostics,2021, 11(1):461-469.
[13] WEN J T,HUANG Z H,LI Q H,et al.Research progress on the tsRNA classification,function,and application in gynecological malignant tumors[J]. Cell Death Discov, 2021,7(1):388.
[14] SAIKIA M,HATZOGLOU M.The many virtues of tRNA-derived stress-induced RNAs (tiRNAs):discovering novel mechanisms of stress response and effect on human health[J]. J Biol Chem,2015,290(50):29761-29768.
[15] DONOVAN J,RATH S,KOLET-MANDRIKOV D,et al.Rapid RNase L-driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery[J]. RNA,2017,23(11):1660-1671.
[16] GARCÍA-CABALLERO D,PÉREZ-MORENO G,ESTÉVEZ A M,et al. Insights into the role of endonuclease V in RNA metabolism in Trypanosoma brucei[J]. Sci Rep,2017,7(1):8505.
[17] NECHOOSHTAN G,YUNUSOV D,CHANG K,et al.Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment[J]. Nucleic Acids Res,2020,48(14):8035-8049.
[18] YANG J Y,DENG X Y,LI Y S,et al.Structure of Schlafen13 reveals a new class of tRNA/rRNA-targeting RNase engaged in translational control[J]. Nat Commun,2018,9(1):1165.
[19] HONDA S,LOHER P,SHIGEMATSU M,et al.Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers[J]. Proc Natl Acad Sci USA,2015,112(29):E3816-E3825.
[20] KUMAR P,KUSCU C,DUTTA A.Biogenesis and function of transfer RNA-related fragments (tRFs)[J]. Trends Biochem Sci,2016,41(8):679-689.
[21] TIAN H H,HU Z Y,WANG C.The therapeutic potential of tRNA-derived small RNAs in neurodegenerative disorders[J]. Aging Dis,2022,13(2):389-401.
[22] VILARDO E,AMMAN F,TOTH U,et al.Functional characterization of the human tRNA methyltransferases TRMT10A and TRMT10B[J]. Nucleic Acids Res,2020, 48(11):6157-6169.
[23] CHEN Z J,QI M J,SHEN B,et al.Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs[J]. Nucleic Acids Res,2019,47(5):2533-2545.
[24] RASHAD S,HAN X B,SATO K,et al.The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation[J]. RNA Biol,2020,17(8):1092-1103.
[25] WANG X Y,MATUSZEK Z,HUANG Y,et al.Queuosine modification protects cognate tRNAs against ribonuclease cleavage[J]. RNA,2018,24(10):1305-1313.
[26] HE Q H,YANG L,GAO K P,et al.FTSJ1 regulates tRNA 2'-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression[J]. Cell Death Dis,2020,11(5):348.
[27] GUZZI N,CIEŚLA M,NGOC P C T,et al. Pseudouridylation of tRNA-derived fragments steers translational control in stem cells[J]. Cell,2018,173(5): 1204-1216.e26.
[28] GUO H P,XIA L,WANG W,et al.Hypoxia induces alterations in tRNA modifications involved in translational control[J]. BMC Biol,2023,21(1):39.
[29] 吴念,代鑫,龚建平. RNA m5C甲基化修饰及其检测技术在肿瘤中的研究进展[J]. 临床医学进展,2022(6):5407-5414.
[30] LEE S,KIM J,VALDMANIS P N,et al.Emerging roles of tRNA-derived small RNAs in cancer biology[J]. Exp Mol Med,2023,55(7):1293-1304.
[31] GREEN J A,ANSARI M Y,BALL H C,et al.tRNA-derived fragments (tRFs) regulate post-transcriptional gene expression via AGO-dependent mechanism in IL-1β stimulated chondrocytes[J]. Osteoarthritis Cartilage,2020, 28(8):1102-1110.
[32] LI X Z,LIU X Y,ZHAO D Z,et al.tRNA-derived small RNAs:novel regulators of cancer hallmarks and targets of clinical application[J]. Cell Death Discov,2021, 7(1):249.
[33] ZHANG Y,GU X L,LI Y,et al.Multiple regulatory roles of the transfer RNA-derived small RNAs in cancers[J]. Genes Dis,2024,11(2):597-613.
[34] LI J,ZHU L,CHENG J,et al.Transfer RNA-derived small RNA:a rising star in oncology[J]. Semin Cancer Biol,2021,75:29-37.
[35] DI FAZIO A,GULLEROVA M.An old friend with a new face:tRNA-derived small RNAs with big regulatory potential in cancer biology[J]. Br J Cancer,2023,128(9): 1625-1635.
[36] FALCONI M,GIANGROSSI M,ZABALETA M E,et al.A novel 3'-tRNA^Glu-derived fragment acts as a tumor suppressor in breast cancer by targeting nucleolin[J]. FASEB J,2019,33(12):13228-13240.
[37] LIU X H,MEI W B,PADMANABAN V,et al. A pro-metastatic tRNA fragment drives Nucleolin oligomerization and stabilization of its bound metabolic mRNAs[J]. Mol Cell,2022,82(14):2604-2617.e8.
[38] HAN L T,LAI H J,YANG Y C,et al.A 5'-tRNA halve,tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer[J]. J Exp Clin Cancer Res,2021,40(1):222.
[39] LYONS S M,KHAREL P,AKIYAMA Y,et al.eIF4G has intrinsic G-quadruplex binding activity that is required for tiRNA function[J]. Nucleic Acids Res,2020, 48(11):6223-6233.
[40] GU X L,ZHANG Y,QIN X Y,et al.Transfer RNA-derived small RNA:an emerging small non-coding RNA with key roles in cancer[J]. Exp Hematol Oncol,2022,11(1):35.
[41] YAN Q,ZHU C M,GUANG S H,et al.The functions of non-coding RNAs in rRNA regulation[J]. Front Genet,2019,10:290.
[42] GEORGE S,RAFI M,ALDARMAKI M,et al.tRNA derived small RNAs-Small players with big roles[J]. Front Genet,2022,13:997780.
[43] ZHANG L O,LIU J,HOU Y.Classification,function,and advances in tsRNA in non-neoplastic diseases[J]. Cell Death Dis,2023,14(11):748.
[44] CHO H,LEE W,KIM G W,et al.Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3' trailer-derived tRNA fragments[J]. Nucleic Acids Res,2019, 47(18):9888-9901.
[45] HE J P,CHEN J K.Epigenetic control of transposable elements and cell fate decision[J]. Yi Chuan,2021, 43(9):822-834.
[46] PANDEY K K,MADHRY D,RAVI KUMAR Y S,et al. Regulatory roles of tRNA-derived RNA fragments in human pathophysiology[J]. Mol Ther Nucleic Acids, 2021,26:161-173.
[47] DI FAZIO A,SCHLACKOW M,PONG S K,et al.Dicer dependent tRNA derived small RNAs promote nascent RNA silencing[J]. Nucleic Acids Res,2022,50(3):1734-1752.
[48] ZHANG Y,GU X L,QIN X Y,et al.Evaluation of serum tRF-23-Q99P9P9NDD as a potential biomarker for the clinical diagnosis of gastric cancer[J]. Mol Med,2022, 28(1):63.
[49] SHEN Y J,XIE Y Y,YU X C,et al.Clinical diagnostic values of transfer RNA-derived fragment tRF-19-3L7L73JD and its effects on the growth of gastric cancer cells[J]. J Cancer,2021,12(11):3230-3238.
[50] ZHU L W,LI Z,YU X C,et al.The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway[J]. Stem Cell Res Ther,2021,12(1):418.
[51] SHEN Y J,YU X C,RUAN Y,et al.Global profile of tRNA-derived small RNAs in gastric cancer patient plasma and identification of tRF-33-P4R8YP9LON4VDP as a new tumor suppressor[J]. Int J Med Sci,2021,18(7): 1570-1579.
[52] WU Y M,YANG X L,JIANG G M,et al.5'-tRF-GlyGCC:a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis[J]. Genome Med,2021,13(1):20.
[53] ZHAN S B,YANG P,ZHOU S K,et al.Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis[J]. Front Med,2022,16(2): 216-226.
[54] CHEN Y M,TANG K T,LIU H J,et al.tRF-His-GTG-1 enhances NETs formation and interferon-α production in lupus by extracellular vesicle[J]. Cell Commun Signal, 2024,22(1):354.
[55] YANG P,ZHANG X S,CHEN S S,et al.A novel serum tsRNA for diagnosis and prediction of nephritis in SLE[J]. Front Immunol,2021,12:735105.
[56] DOU R,ZHANG X L,XU X D,et al.Mesenchymal stem cell exosomal tsRNA-21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization[J]. Mol Immunol,2021,139:106-114.
[57] HUANG P,TU B,LIAO H J,et al.Elevation of plasma tRNA fragments as a promising biomarker for liver fibrosis in nonalcoholic fatty liver disease[J]. Sci Rep, 2021,11(1):5886.
[58] ZHANG Y F,ZHANG Y,SHI J C,et al.Identification and characterization of an ancient class of small RNAs enriched in serum associating with active infection[J]. J Mol Cell Biol,2014,6(2):172-174.

Advances in the Generation and Biological Function of tsRNAs

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