Skip to main content
SpringerLink
Log in

tRNA-derived fragments (tRFs): establishing their turf in post-transcriptional gene regulation

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Transfer RNA (tRNA)-derived fragments (tRFs) are an emerging class of conserved small non-coding RNAs that play important roles in post-transcriptional gene regulation. High-throughput sequencing of multiple biological samples have identified heterogeneous species of tRFs with distinct functionalities. These small RNAs have garnered a lot of scientific attention due to their ubiquitous expression and versatility in regulating various biological processes. In this review, we highlight our current understanding of tRF biogenesis and their regulatory functions. We summarize the diverse modes of biogenesis through which tRFs are generated and discuss the mechanism through which different tRF species regulate gene expression and the biological implications. Finally, we conceptualize research areas that require focus to strengthen our understanding of the biogenesis and function of tRFs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Thompson DM, Parker R (2009) Stressing Out over tRNA Cleavage. Cell. https://doi.org/10.1016/j.cell.2009.07.001

    Article  PubMed  PubMed Central  Google Scholar 

  2. Speer J, Gehrke CW, Kuo KC, Waalkes TP, Borek E (1979) tRNA breakdown products as markers for cancer. Cancer. https://doi.org/10.1002/1097-0142(197912)44:6%3c2120::AID-CNCR2820440623%3e3.0.CO;2-6

    Article  PubMed  Google Scholar 

  3. Tomita K, Ogawa T, Uozumi T, Watanabe K, Masaki H (2000) A cytotoxic ribonuclease which specifically cleaves four isoaccepting arginine tRNAs at their anticodon loops. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.140213797

    Article  PubMed  Google Scholar 

  4. Levitz R, Chapman D, Amitsur M, Green R, Snyder L, Kaufmann G (1990) The optional E. coli prr locus encodes a latent form of phage T4-induced anticodon nuclease. EMBO J 9:1383

    Article  CAS  Google Scholar 

  5. Keam S, Hutvagner G (2015) tRNA-Derived Fragments (tRFs): emerging new roles for an ancient RNA in the regulation of gene expression. Life 5:1638–1651

    Article  CAS  Google Scholar 

  6. Chen Q, Yan M, Cao Z, Li X, Zhang YY, Shi J, Feng GHG-h, Peng H, Zhang X, Zhang YY et al (2016) Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351:397–400

    Article  CAS  Google Scholar 

  7. Krishna S, Yim DG, Lakshmanan V, Tirumalai V, Koh JL, Park JE, Cheong JK, Low JL, Lim MJ, Sze SK et al (2019) Dynamic expression of tRNA‐derived small RNAs define cellular states. EMBO Rep. https://doi.org/10.15252/embr.201947789

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, Belleannee C, Kucukural A, Serra RW, Sun F et al (2016) Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science (80-) 351:391–396

    Article  CAS  Google Scholar 

  9. Honda S, Loher P, Shigematsu M, Palazzo JP, Suzuki R, Imoto I, Rigoutsos I, Kirino Y (2015) Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers. Proc Natl Acad Sci U S A 112:E3816–E3825

    Article  CAS  Google Scholar 

  10. Guzzi N, Cieśla M, Ngoc PCT, Lang S, Arora S, Dimitriou M, Pimková K, Sommarin MNE, Munita R, Lubas M et al (2018) Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells. Cell. https://doi.org/10.1016/j.cell.2018.03.008

    Article  PubMed  Google Scholar 

  11. Luo S, He F, Luo J, Dou S, Wang Y, Guo A, Lu J (2018) Drosophila tsRNAs preferentially suppress general translation machinery via antisense pairing and participate in cellular starvation response. Nucleic Acids Res. https://doi.org/10.1093/nar/gky189

    Article  PubMed  PubMed Central  Google Scholar 

  12. Su Z, Kuscu C, Malik A, Shibata E, Dutta A (2019) Angiogenin generates specific stress-induced tRNA halves and is not involved in tRF-3-mediated gene silencing. J Biol Chem. https://doi.org/10.1074/jbc.ra119.009272

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yamasaki S, Ivanov P, Hu GF, Anderson P (2009) Angiogenin cleaves tRNA and promotes stress-induced translational repression. J Cell Biol 185:35–42

    Article  CAS  Google Scholar 

  14. Goodarzi H, Liu X, Nguyen HCB, Zhang S, Fish L, Tavazoie SF (2015) Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell 161:790–802

    Article  CAS  Google Scholar 

  15. Lee YS, Shibata Y, Malhotra A, Dutta A (2009) A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 23:2639–2649

    Article  CAS  Google Scholar 

  16. Torres AG, Reina O, Attolini CSO, De Pouplana LR (2019) Differential expression of human tRNA genes drives the abundance of tRNA-derived fragments. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1821120116

    Article  PubMed  Google Scholar 

  17. Saxena SK, Rybak SM, Davey RT, Youle RJ, Ackerman EJ (1992) Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily. J Biol Chem 267(30):21982–21986

    Article  CAS  Google Scholar 

  18. Fu H, Feng J, Liu Q, Sun F, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2009) Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett 583:437–442

    Article  CAS  Google Scholar 

  19. Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P (2011) Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell 43:613–623

    Article  CAS  Google Scholar 

  20. Pizzo E, Sarcinelli C, Sheng J, Fusco S, Formiggini F, Netti P, Yu W, D’Alessio G, Hu G-F (2013) Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin to control growth and survival. J Cell Sci. https://doi.org/10.1242/jcs.134551

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sharma U, Sun F, Conine CC, Reichholf B, Kukreja S, Herzog VA, Ameres SL, Rando OJ (2018) Small RNAs are trafficked from the epididymis to developing mammalian sperm. Dev Cell. https://doi.org/10.1016/j.devcel.2018.06.023

    Article  PubMed  PubMed Central  Google Scholar 

  22. Andersen KL, Collins K (2012) Several RNase T2 enzymes function in induced tRNA and rRNA turnover in the ciliate Tetrahymena. Mol Biol Cell. https://doi.org/10.1091/mbc.E11-08-0689

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hsieh LC, Lin SI, Shih ACC, Chen JW, Lin WY, Tseng CY, Li WH, Chiou TJ (2009) Uncovering small RNA-mediated responses to phosphate deficiency in Arabidopsis by deep sequencing. Plant Physiol. https://doi.org/10.1104/pp.109.147280

    Article  PubMed  PubMed Central  Google Scholar 

  24. Megel C, Hummel G, Lalande S, Ubrig E, Cognat V, Morelle G, Salinas-Giegé T, Duchêne AM, Maréchal-Drouard L (2019) Plant RNases T2, but not Dicer-like proteins, are major players of tRNA-derived fragments biogenesis. Nucleic Acids Res. https://doi.org/10.1093/nar/gky1156

    Article  PubMed  Google Scholar 

  25. Donovan J, Rath S, Kolet-Mandrikov D, Korennykh A (2017) Rapid RNase L–driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery. RNA. https://doi.org/10.1261/rna.062000.117

    Article  PubMed  PubMed Central  Google Scholar 

  26. García-Caballero D, Pérez-Moreno G, Estévez AM, Ruíz-Pérez LM, Vidal AE, González-Pacanowska D (2017) Insights into the role of endonuclease v in RNA metabolism in Trypanosoma brucei. Sci Rep. https://doi.org/10.1038/s41598-017-08910-1

    Article  PubMed  PubMed Central  Google Scholar 

  27. Nechooshtan G, Yunusov D, Chang K, Gingeras TR (2020) Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment. Nucleic Acids Res. https://doi.org/10.1093/nar/gkaa526

    Article  PubMed  PubMed Central  Google Scholar 

  28. Cole C, Sobala A, Lu C, Thatcher SR, Bowman A, Brown JWS, Green PJ, Barton GJ, Hutvagner G (2009) Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA 15:2147–2160

    Article  CAS  Google Scholar 

  29. Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, Livingston DM, Rajewsky K (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. https://doi.org/10.1101/gad.1248505

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pereira M, Francisco S, Varanda AS, Santos M, Santos MAS, Soares AR (2018) Impact of tRNA modifications and tRNA-modifying enzymes on proteostasis and human disease. Int J Mol Sci. https://doi.org/10.3390/ijms19123738

    Article  PubMed  PubMed Central  Google Scholar 

  31. Blanco S, Dietmann S, Flores JV, Hussain S, Kutter C, Humphreys P, Lukk M, Lombard P, Treps L, Popis M et al (2014) Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J. https://doi.org/10.15252/embj.201489282

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wang X, Matuszek Z, Huang Y, Parisien M, Dai Q, Clark W, Schwartz MH, Pan T (2018) Queuosine modification protects cognate tRNAs against ribonuclease cleavage. RNA. https://doi.org/10.1261/rna.067033.118

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chen Z, Qi M, Shen B, Luo G, Wu Y, Li J, Lu Z, Zheng Z, Dai Q, Wang H (2019) Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs. Nucleic Acids Res. https://doi.org/10.1093/nar/gky1250

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tuorto F, Liebers R, Musch T, Schaefer M, Hofmann S, Kellner S, Frye M, Helm M, Stoecklin G, Lyko F (2012) RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol. https://doi.org/10.1038/nsmb.2357

    Article  PubMed  Google Scholar 

  35. Frye M, Harada BT, Behm M, He C (2018) RNA modifications modulate gene expression during development. Science. https://doi.org/10.1126/science.aau1646

    Article  PubMed  PubMed Central  Google Scholar 

  36. Alemu E, He C, Klungland A (2016) ALKBHs-facilitated RNA modifications and de-modifications. DNA Repair (Amst). https://doi.org/10.1016/j.dnarep.2016.05.026

    Article  Google Scholar 

  37. Fergus C, Barnes D, Alqasem MA, Kelly VP (2015) The queuine micronutrient: charting a course from microbe to man. Nutrients. https://doi.org/10.3390/nu7042897

    Article  PubMed  PubMed Central  Google Scholar 

  38. Gkatza NA, Castro C, Harvey RF, Heiß M, Popis MC, Blanco S, Bornelöv S, Sajini AA, Gleeson JG, Griffin JL et al (2019) Cytosine-5 RNA methylation links protein synthesis to cell metabolism. PLoS Biol. https://doi.org/10.1371/journal.pbio.3000297

    Article  PubMed  PubMed Central  Google Scholar 

  39. Frigolé HR, Camacho N, Coma MC, Fernández-Lozano C, García-Lema J, Rafels-Ybern À, Canals A, Coll M, de Pouplana LR (2019) TRNA deamination by ADAT requires substrate-specific recognition mechanisms and can be inhibited by tRFs. RNA. https://doi.org/10.1261/rna.068189.118

    Article  Google Scholar 

  40. Drino A, Oberbauer V, Troger C, Janisiw E, Anrather D, Hartl M, Kaiser S, Kellner S, Schaefer MR (2020) Production and purification of endogenously modified tRNA-derived small RNAs. RNA Biol. https://doi.org/10.1080/15476286.2020.1733798

    Article  PubMed  PubMed Central  Google Scholar 

  41. Akiyama Y, Kharel P, Abe T, Anderson P, Ivanov P (2020) Isolation and initial structure-functional characterization of endogenous tRNA-derived stress-induced RNAs. RNA Biol. https://doi.org/10.1080/15476286.2020.1732702

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lyons SM, Gudanis D, Coyne SM, Gdaniec Z, Ivanov P (2017) Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs. Nat Commun 8(1):1–11

    Article  Google Scholar 

  43. Sobala A, Hutvagner G (2013) Small RNAs derived from the 5’ end of tRNA can inhibit protein translation in human cells. RNA Biol 10:553–563

    Article  CAS  Google Scholar 

  44. Gebetsberger J, Wyss L, Mleczko AM, Reuther J, Polacek N (2017) A tRNA-derived fragment competes with mRNA for ribosome binding and regulates translation during stress. RNA Biol. https://doi.org/10.1080/15476286.2016.1257470

    Article  PubMed  Google Scholar 

  45. Maute RL, Schneider C, Sumazin P, Holmes A, Califano A, Basso K, Dalla-Favera R (2013) TRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1206761110

    Article  PubMed  Google Scholar 

  46. Kumar P, Anaya J, Mudunuri SB, Dutta A (2014) Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets. BMC Med 12:1

    Article  CAS  Google Scholar 

  47. Couvillion MT, Bounova G, Purdom E, Speed TP, Collins K (2012) A Tetrahymena Piwi Bound to Mature tRNA 3’ Fragments Activates the Exonuclease Xrn2 for RNA Processing in the Nucleus. Mol Cell. https://doi.org/10.1016/j.molcel.2012.09.010

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lakshmanan V, Bansal D, Sujith TN, Shivaprasad PV, Palakodeti D, Krishna S (2020) Comprehensive annotation and characterization of planarian tRNA and tRNA-derived fragments (tRFs). bioRxiv. https://doi.org/10.1101/2020.08.25.266106

    Article  Google Scholar 

  49. Keam SP, Young PE, McCorkindale AL, Dang THY, Clancy JL, Humphreys DT, Preiss T, Hutvagner G, Martin DIK, Cropley JE et al (2014) The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic Acids Res. https://doi.org/10.1093/nar/gku620

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kim HK, Fuchs G, Wang S, Wei W, Zhang Y, Park H, Roy-Chaudhuri B, Li P, Xu J, Chu K et al (2017) A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature. https://doi.org/10.1038/nature25005

    Article  PubMed  PubMed Central  Google Scholar 

  51. Schorn AJ, Gutbrod MJ, LeBlanc C, Martienssen R (2017) LTR-Retrotransposon Control by tRNA-Derived Small RNAs. Cell 170:61-71.e11

    Article  CAS  Google Scholar 

  52. Zhang Y, Zhang X, Shi J, Tuorto F, Li X, Liu Y, Liebers R, Zhang L, Qu Y, Qian J et al (2018) Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nat Cell Biol. https://doi.org/10.1038/s41556-018-0087-2

    Article  PubMed  PubMed Central  Google Scholar 

  53. Thompson DM, Lu C, Green PJ, Parker R (2008) tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA 14:2095–2103

    Article  CAS  Google Scholar 

  54. Karaiskos S, Naqvi AS, Swanson KE, Grigoriev A (2015) Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets. Biol Direct. https://doi.org/10.1186/s13062-015-0081-6

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lee SR, Collins K (2005) Starvation-induced cleavage of the tRNA anticodon loop in Tetrahymena thermophila. J Biol Chem 280:42744–42749

    Article  CAS  Google Scholar 

  56. Saikia M, Krokowski D, Guan BJ, Ivanov P, Parisien M, Hu GF, Anderson P, Pan T, Hatzoglou M (2012) Genome-wide identification and quantitative analysis of cleaved tRNA fragments induced by cellular stress. J Biol Chem. https://doi.org/10.1074/jbc.M112.371799

    Article  PubMed  PubMed Central  Google Scholar 

  57. Emara MM, Ivanov P, Hickman T, Dawra N, Tisdale S, Kedersha N, Hu GF, Anderson P (2010) Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress granule assembly. J Biol Chem 285:10959–10968

    Google Scholar 

  58. Saikia M, Jobava R, Parisien M, Putnam A, Krokowski D, Gao X-H, Guan B-J, Yuan Y, Jankowsky E, Feng Z et al (2014) Angiogenin-Cleaved tRNA Halves Interact with Cytochrome c, Protecting Cells from Apoptosis during Osmotic Stress. Mol Cell Biol. https://doi.org/10.1128/MCB.00136-14

    Article  PubMed  PubMed Central  Google Scholar 

  59. Yeri A, Courtright A, Reiman R, Carlson E, Beecroft T, Janss A, Siniard A, Richholt R, Balak C, Rozowsky J et al (2017) Total extracellular small RNA profiles from plasma, saliva, and urine of healthy subjects. Sci Rep. https://doi.org/10.1038/srep44061

    Article  PubMed  PubMed Central  Google Scholar 

  60. Magee RG, Telonis AG, Loher P, Londin E, Rigoutsos I (2018) Profiles of miRNA Isoforms and tRNA Fragments in Prostate Cancer. Sci Rep. https://doi.org/10.1038/s41598-018-22488-2

    Article  PubMed  PubMed Central  Google Scholar 

  61. Dhahbi JM, Spindler SR, Atamna H, Yamakawa A, Boffelli D, Mote P, Martin DIK (2013) 5’ tRNA halves are present as abundant complexes in serum, concentrated in blood cells, and modulated by aging and calorie restriction. BMC Genomics. https://doi.org/10.1186/1471-2164-14-298

    Article  PubMed  PubMed Central  Google Scholar 

  62. Zhang Y, Zhang Y, Shi J, Zhang H, Cao Z, Gao X, Ren W, Ning Y, Ning L, Cao Y et al (2014) Identification and characterization of an ancient class of small RNAs enriched in serum associating with active infection. J Mol Cell Biol. https://doi.org/10.1093/jmcb/mjt052

    Article  PubMed  PubMed Central  Google Scholar 

  63. Wu X, Somlo G, Yu Y, Palomares MR, Li AX, Zhou W, Chow A, Yen Y, Rossi JJ, Gao H et al (2012) De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. J Transl Med. https://doi.org/10.1186/1479-5876-10-42

    Article  PubMed  PubMed Central  Google Scholar 

  64. Martinez BV, Dhahbi JM, Nunez Lopez YO, Lamperska K, Golusinski P, Luczewski L, Kolenda T, Atamna H, Spindler SR, Golusinski W et al (2015) Circulating small non coding RNA signature in head and neck squamous cell carcinoma. Oncotarget. https://doi.org/10.18632/oncotarget.4266

    Article  PubMed  PubMed Central  Google Scholar 

  65. Zhao C, Tolkach Y, Schmidt D, Kristiansen G, Müller SC, Ellinger J (2018) 5′-tRNA halves are dysregulated in clear cell renal cell carcinoma. J Urol. https://doi.org/10.1016/j.juro.2017.07.082

    Article  PubMed  Google Scholar 

  66. Zhao C, Tolkach Y, Schmidt D, Muders M, Kristiansen G, Müller SC, Ellinger J (2018) tRNA-halves are prognostic biomarkers for patients with prostate cancer. Urol Oncol Semin Orig Investig. https://doi.org/10.1016/j.urolonc.2018.08.003

    Article  Google Scholar 

  67. Tosar JP, Gámbaro F, Darré L, Pantano S, Westhof E, Cayota A (2018) Dimerization confers increased stability to nucleases in 5 halves from glycine and glutamic acid tRNAs. Nucleic Acids Res. https://doi.org/10.1093/nar/gky495

    Article  PubMed  PubMed Central  Google Scholar 

  68. Tosar JP, Segovia M, Castellano M, Gámbaro F, Akiyama Y, Fagúndez P, Olivera Á, Costa B, Possi T, Hill M et al (2020) Fragmentation of extracellular ribosomes and tRNAs shapes the extracellular RNAome. Nucleic Acids Res. https://doi.org/10.1093/nar/gkaa674

    Article  PubMed  PubMed Central  Google Scholar 

  69. Cheong JK, Nguyen TH, Wang H, Tan P, Voorhoeve PM, Lee SH, Virshup DM (2011) IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1δ/ɛ and Wnt/β-catenin independent inhibition of mitotic spindle formation. Oncogene 30:2558–2569

    Article  CAS  Google Scholar 

  70. Huang B, Yang H, Cheng X, Wang D, Fu S, Shen W, Zhang Q, Zhang L, Xue Z, Li Y et al (2017) TRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-16-3146

    Article  PubMed  PubMed Central  Google Scholar 

  71. Shao Y, Sun Q, Liu X, Wang P, Wu R, Ma Z (2017) tRF-Leu-CAG promotes cell proliferation and cell cycle in non-small cell lung cancer. Chem Biol Drug Des. https://doi.org/10.1111/cbdd.12994

    Article  PubMed  PubMed Central  Google Scholar 

  72. Sheng J, Xu Z (2016) Three decades of research on angiogenin: A review and perspective. Acta Biochim Biophys Sin (Shanghai). https://doi.org/10.1093/abbs/gmv131

    Article  Google Scholar 

  73. Peng H, Shi J, Zhang Y, Zhang H, Liao S, Li W, Lei L, Han C, Ning L, Cao Y et al (2012) A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm. Cell Res 22:1609–1612

    Article  CAS  Google Scholar 

  74. Sarker G, Sun W, Rosenkranz D, Pelczar P, Opitz L, Efthymiou V, Wolfrum C, Peleg-Raibstein D (2019) Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1820810116

    Article  PubMed  Google Scholar 

  75. Van Es MA, Schelhaas HJ, Van Vught PWJ, Ticozzi N, Andersen PM, Groen EJN, Schulte C, Blauw HM, Koppers M, Diekstra FP et al (2011) Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. Ann Neurol. https://doi.org/10.1002/ana.22611

    Article  PubMed  PubMed Central  Google Scholar 

  76. Greenway MJ, Andersen PM, Russ G, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J et al (2006) ANG mutations segregate with familial and ‘sporadic’ amyotrophic lateral sclerosis. Nat Genet. https://doi.org/10.1038/ng1742

    Article  PubMed  Google Scholar 

  77. Ivanov P, O’Day E, Emara MM, Wagner G, Lieberman J, Anderson P (2014) G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1407361111

    Article  PubMed  Google Scholar 

  78. Zhang S, Sun L, Kragler F (2009) The phloem-delivered RNA pool contains small noncoding RNAs and interferes with translation1[W][OA]. Plant Physiol. https://doi.org/10.1104/pp.108.134767

    Article  PubMed  PubMed Central  Google Scholar 

  79. Ren B, Wang X, Duan J, Ma J (2019) Rhizobial tRNA-derived small RNAs are signal molecules regulating plant nodulation. Science (80-). https://doi.org/10.1126/science.aav8907

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge all the research groups who have contributed towards understanding tRNA-derived fragments. DP thanks DST-Swarnajayanti (DST/SJF/LSA-02/2015-16) and inStem core funds. SR is funded through DBT Grant BT/PR31418/BRB/10/1758/2019 and inStem core funds. RD was supported by core funds from A*STAR.

Author information

Authors and Affiliations

  1. Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India

    Srikar Krishna, Srikala Raghavan & Dasaradhi Palakodeti

  2. SASTRA University, Thirumalaisamudram, Thanjavur, India

    Srikar Krishna

  3. Precision Oncology, Genome Institute of Singapore, Singapore City, Singapore

    Ramanuj DasGupta

Authors
  1. Srikar Krishna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Srikala Raghavan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ramanuj DasGupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dasaradhi Palakodeti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Srikala Raghavan, Ramanuj DasGupta or Dasaradhi Palakodeti.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krishna, S., Raghavan, S., DasGupta, R. et al. tRNA-derived fragments (tRFs): establishing their turf in post-transcriptional gene regulation. Cell. Mol. Life Sci. 78, 2607–2619 (2021). https://doi.org/10.1007/s00018-020-03720-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-020-03720-7

Keywords

Search

Navigation