1932

Abstract

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.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-022620-101840
2020-11-23
2024-07-15
Loading full text...

Full text loading...

/deliver/fulltext/genet/54/1/annurev-genet-022620-101840.html?itemId=/content/journals/10.1146/annurev-genet-022620-101840&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Al-Shayeb B, Sachdeva R, Chen LX, Ward F, Munk P et al. 2020. Clades of huge phages from across Earth's ecosystems. Nature 578:425–31
    [Google Scholar]
  2. 2. 
    Balatti V, Nigita G, Veneziano D, Drusco A, Stein GS et al. 2017. tsRNA signatures in cancer. PNAS 114:8071–76
    [Google Scholar]
  3. 3. 
    Balatti V, Rizzotto L, Miller C, Palamarchuk A, Fadda P et al. 2015. TCL1 targeting miR-3676 is codeleted with tumor protein p53 in chronic lymphocytic leukemia. PNAS 112:2169–74
    [Google Scholar]
  4. 4. 
    Bellezza I, Peirce MJ, Minelli A 2014. Cyclic dipeptides: from bugs to brain. Trends Mol. Med. 20:551–58
    [Google Scholar]
  5. 5. 
    Berg MD, Giguere DJ, Dron JS, Lant JT, Genereaux J et al. 2019. Targeted sequencing reveals expanded genetic diversity of human transfer RNAs. RNA Biol 16:1574–85
    [Google Scholar]
  6. 6. 
    Blanco S, Dietmann S, Flores JV, Hussain S, Kutter C et al. 2014. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J 33:2020–39
    [Google Scholar]
  7. 7. 
    Boccaletto P, Machnicka MA, Purta E, Piatkowski P, Baginski B et al. 2018. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res 46:D303–7
    [Google Scholar]
  8. 8. 
    Bolton EC, Boeke JD. 2003. Transcriptional interactions between yeast tRNA genes, flanking genes and Ty elements: a genomic point of view. Genome Res 13:254–63
    [Google Scholar]
  9. 9. 
    Boskovic A, Bing XY, Kaymak E, Rando OJ 2020. Control of noncoding RNA production and histone levels by a 5′ tRNA fragment. Genes Dev 34:118–31
    [Google Scholar]
  10. 10. 
    Bracha D, Walls MT, Brangwynne CP 2019. Probing and engineering liquid-phase organelles. Nat. Biotechnol. 37:1435–45
    [Google Scholar]
  11. 11. 
    Carone BR, Fauquier L, Habib N, Shea JM, Hart CE et al. 2010. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143:1084–96
    [Google Scholar]
  12. 12. 
    Chen Q, Yan M, Cao Z, Li X, Zhang Y et al. 2016. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351:397–400
    [Google Scholar]
  13. 13. 
    Chen Z, Qi M, Shen B, Luo G, Wu Y et al. 2019. Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs. Nucleic Acids Res 47:2533–45
    [Google Scholar]
  14. 14. 
    Chin JW. 2014. Expanding and reprogramming the genetic code of cells and animals. Annu. Rev. Biochem. 83:379–408
    [Google Scholar]
  15. 15. 
    Chiou NT, Kageyama R, Ansel KM 2018. Selective export into extracellular vesicles and function of tRNA fragments during T cell activation. Cell Rep 25:3356–70.e4
    [Google Scholar]
  16. 16. 
    Cho H, Lee W, Kim GW, Lee SH, Moon JS et al. 2019. Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3′ trailer-derived tRNA fragments. Nucleic Acids Res 47:9888–901
    [Google Scholar]
  17. 17. 
    Cosentino C, Toivonen S, Diaz Villamil E, Atta M, Ravanat JL et al. 2018. Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes. Nucleic Acids Res 46:10302–18
    [Google Scholar]
  18. 18. 
    Couvillion MT, Sachidanandam R, Collins K 2010. A growth-essential Tetrahymena Piwi protein carries tRNA fragment cargo. Genes Dev 24:2742–47
    [Google Scholar]
  19. 19. 
    Dhahbi JM. 2015. 5′ tRNA halves: the next generation of immune signaling molecules. Front. Immunol. 6:74
    [Google Scholar]
  20. 20. 
    Dong J, Qiu H, Garcia-Barrio M, Anderson J, Hinnebusch AG 2000. Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain. Mol. Cell 6:269–79
    [Google Scholar]
  21. 21. 
    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 23:1660–71
    [Google Scholar]
  22. 22. 
    Donze D, Kamakaka RT. 2001. RNA polymerase III and RNA polymerase II promoter complexes are heterochromatin barriers in Saccharomyces cerevisiae. . EMBO J 20:520–31
    [Google Scholar]
  23. 23. 
    Duan Z, Andronescu M, Schutz K, McIlwain S, Kim YJ et al. 2010. A three-dimensional model of the yeast genome. Nature 465:363–67
    [Google Scholar]
  24. 24. 
    Dubey RN, Gartenberg MR. 2007. A tDNA establishes cohesion of a neighboring silent chromatin domain. Genes Dev 21:2150–60
    [Google Scholar]
  25. 25. 
    Durdevic Z, Mobin MB, Hanna K, Lyko F, Schaefer M 2013. The RNA methyltransferase Dnmt2 is required for efficient Dicer-2-dependent siRNA pathway activity in Drosophila. . Cell Rep 4:931–37
    [Google Scholar]
  26. 26. 
    Eigenbrod T, Dalpke AH. 2015. Bacterial RNA: an underestimated stimulus for innate immune responses. J. Immunol. 195:411–18
    [Google Scholar]
  27. 27. 
    Fields RN, Roy H. 2018. Deciphering the tRNA-dependent lipid aminoacylation systems in bacteria: novel components and structural advances. RNA Biol 15:480–91
    [Google Scholar]
  28. 28. 
    Francklyn CS, Minajigi A. 2010. tRNA as an active chemical scaffold for diverse chemical transformations. FEBS Lett 584:366–75
    [Google Scholar]
  29. 29. 
    Freund I, Buhl DK, Boutin S, Kotter A, Pichot F et al. 2019. 2′-O-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal Toll-like receptors but does not affect recognition of whole organisms. RNA 25:869–80
    [Google Scholar]
  30. 30. 
    Fricker R, Brogli R, Luidalepp H, Wyss L, Fasnacht M et al. 2019. A tRNA half modulates translation as stress response in Trypanosoma brucei. Nat. Commun 10:118
    [Google Scholar]
  31. 31. 
    Garcia-Perez JL, Widmann TJ, Adams IR 2016. The impact of transposable elements on mammalian development. Development 143:4101–14
    [Google Scholar]
  32. 32. 
    Gehrig S, Eberle ME, Botschen F, Rimbach K, Eberle F et al. 2012. Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity. J. Exp. Med. 209:225–33
    [Google Scholar]
  33. 33. 
    Geslain R, Pan T. 2010. Functional analysis of human tRNA isodecoders. J. Mol. Biol. 396:821–31
    [Google Scholar]
  34. 34. 
    Gkatza NA, Castro C, Harvey RF, Heiss M, Popis MC et al. 2019. Cytosine-5 RNA methylation links protein synthesis to cell metabolism. PLOS Biol 17:e3000297
    [Google Scholar]
  35. 35. 
    Godoy PM, Bhakta NR, Barczak AJ, Cakmak H, Fisher S et al. 2018. Large differences in small RNA composition between human biofluids. Cell Rep 25:1346–58
    [Google Scholar]
  36. 36. 
    Gogakos T, Brown M, Garzia A, Meyer C, Hafner M, Tuschl T 2017. Characterizing expression and processing of precursor and mature human tRNAs by hydro-tRNAseq and PAR-CLIP. Cell Rep 20:1463–75
    [Google Scholar]
  37. 37. 
    Goodarzi H, Liu X, Nguyen HC, Zhang S, Fish L, Tavazoie SF 2015. Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell 161:790–802
    [Google Scholar]
  38. 38. 
    Goodarzi H, Nguyen HCB, Zhang S, Dill BD, Molina H, Tavazoie SF 2016. Modulated expression of specific tRNAs drives gene expression and cancer progression. Cell 165:1416–27
    [Google Scholar]
  39. 39. 
    Guzzi N, Ciesla M, Ngoc PCT, Lang S, Arora S et al. 2018. Pseudouridylation of tRNA-derived fragments steers translational control in stem cells. Cell 173:1204–16.e26
    [Google Scholar]
  40. 40. 
    Hamdani O, Dhillon N, Hsieh TS, Fujita T, Ocampo J et al. 2019. tRNA genes affect chromosome structure and function via local effects. Mol. Cell. Biol. 39:e00432–18
    [Google Scholar]
  41. 41. 
    Hanada T, Weitzer S, Mair B, Bernreuther C, Wainger BJ et al. 2013. CLP1 links tRNA metabolism to progressive motor-neuron loss. Nature 495:474–80
    [Google Scholar]
  42. 42. 
    Hasler D, Lehmann G, Murakawa Y, Klironomos F, Jakob L et al. 2016. The Lupus autoantigen La prevents mis-channeling of tRNA fragments into the human microRNA pathway. Mol. Cell 63:110–24
    [Google Scholar]
  43. 43. 
    Henkin TM. 2014. The T box riboswitch: a novel regulatory RNA that utilizes tRNA as its ligand. Biochim. Biophys. Acta 1839:959–63
    [Google Scholar]
  44. 44. 
    Honda S, Kawamura T, Loher P, Morichika K, Rigoutsos I, Kirino Y 2017. The biogenesis pathway of tRNA-derived piRNAs in Bombyx germ cells. Nucleic Acids Res 45:9108–20
    [Google Scholar]
  45. 45. 
    Honda S, Loher P, Shigematsu M, Palazzo JP, Suzuki R et al. 2015. Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers. PNAS 112:E3816–25
    [Google Scholar]
  46. 46. 
    Huang B, Yang H, Cheng X, Wang D, Fu S et al. 2017. tRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer. Cancer Res 77:3194–206
    [Google Scholar]
  47. 47. 
    Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P 2011. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol. Cell 43:613–23
    [Google Scholar]
  48. 48. 
    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. PNAS 111:18201–6
    [Google Scholar]
  49. 49. 
    Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q et al. 2019. Reassessment of exosome composition. Cell 177:428–45.e18
    [Google Scholar]
  50. 50. 
    Jin D, Musier-Forsyth K. 2019. Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication. J. Biol. Chem. 294:5352–64
    [Google Scholar]
  51. 51. 
    Jockel S, Nees G, Sommer R, Zhao Y, Cherkasov D et al. 2012. The 2′-O-methylation status of a single guanosine controls transfer RNA–mediated Toll-like receptor 7 activation or inhibition. J. Exp. Med. 209:235–41
    [Google Scholar]
  52. 52. 
    Kamhi E, Raitskin O, Sperling R, Sperling J 2010. A potential role for initiator-tRNA in pre-mRNA splicing regulation. PNAS 107:11319–24
    [Google Scholar]
  53. 53. 
    Karaca E, Weitzer S, Pehlivan D, Shiraishi H, Gogakos T et al. 2014. Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function. Cell 157:636–50
    [Google Scholar]
  54. 54. 
    Katibah GE, Lee HJ, Huizar JP, Vogan JM, Alber T, Collins K 2013. tRNA binding, structure, and localization of the human interferon-induced protein IFIT5. Mol. Cell 49:743–50
    [Google Scholar]
  55. 55. 
    Katz A, Elgamal S, Rajkovic A, Ibba M 2016. Non-canonical roles of tRNAs and tRNA mimics in bacterial cell biology. Mol. Microbiol. 101:545–58
    [Google Scholar]
  56. 56. 
    Keam SP, Young PE, McCorkindale AL, Dang TH, Clancy JL et al. 2014. The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic Acids Res 42:8984–95
    [Google Scholar]
  57. 57. 
    Keller P, Freund I, Marchand V, Bec G, Huang R et al. 2018. Double methylation of tRNA-U54 to 2′-O-methylthymidine (Tm) synergistically decreases immune response by Toll-like receptor 7. Nucleic Acids Res 46:9764–75
    [Google Scholar]
  58. 58. 
    Kim HK, Fuchs G, Wang S, Wei W, Zhang Y et al. 2017. A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature 552:57–62
    [Google Scholar]
  59. 59. 
    Kim JM, Seok OH, Ju S, Heo JE, Yeom J et al. 2018. Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway. Science 362:eaat0174
    [Google Scholar]
  60. 60. 
    Kirchner S, Ignatova Z. 2015. Emerging roles of tRNA in adaptive translation, signalling dynamics and disease. Nat. Rev. Genet. 16:98–112
    [Google Scholar]
  61. 61. 
    Knapp D, Michaels YS, Jamilly M, Ferry QRV, Barbosa H et al. 2019. Decoupling tRNA promoter and processing activities enables specific Pol-II Cas9 guide RNA expression. Nat. Commun. 10:1490
    [Google Scholar]
  62. 62. 
    Krishna S, Yim DG, Lakshmanan V, Tirumalai V, Koh JL et al. 2019. Dynamic expression of tRNA-derived small RNAs define cellular states. EMBO Rep 20:e47789
    [Google Scholar]
  63. 63. 
    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 Biol 12:78
    [Google Scholar]
  64. 64. 
    Kumar P, Kuscu C, Dutta A 2016. Biogenesis and function of transfer RNA-related fragments (tRFs). Trends Biochem. Sci. 41:679–89
    [Google Scholar]
  65. 65. 
    Kumar P, Mudunuri SB, Anaya J, Dutta A 2015. tRFdb: a database for transfer RNA fragments. Nucleic Acids Res 43:D141–45
    [Google Scholar]
  66. 66. 
    Kuscu C, Kumar P, Kiran M, Su Z, Malik A, Dutta A 2018. tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA 24:1093–105
    [Google Scholar]
  67. 67. 
    LaRiviere FJ, Wolfson AD, Uhlenbeck OC 2001. Uniform binding of aminoacyl-tRNAs to elongation factor Tu by thermodynamic compensation. Science 294:165–68
    [Google Scholar]
  68. 68. 
    Lee YS, Shibata Y, Malhotra A, Dutta A 2009. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 23:2639–49
    [Google Scholar]
  69. 69. 
    Li M, Kao E, Gao X, Sandig H, Limmer K et al. 2012. Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11. Nature 491:125–28
    [Google Scholar]
  70. 70. 
    Li M, Kao E, Malone D, Gao X, Wang JYJ, David M 2018. DNA damage-induced cell death relies on SLFN11-dependent cleavage of distinct type II tRNAs. Nat. Struct. Mol. Biol. 25:1047–58
    [Google Scholar]
  71. 71. 
    Li X, Fu XD. 2019. Chromatin-associated RNAs as facilitators of functional genomic interactions. Nat. Rev. Genet. 20:503–19
    [Google Scholar]
  72. 72. 
    Liu C, Stonestrom AJ, Christian T, Yong J, Takase R et al. 2016. Molecular basis and consequences of the cytochrome c-tRNA interaction. J. Biol. Chem. 291:10426–36
    [Google Scholar]
  73. 73. 
    Liu F, Clark W, Luo G, Wang X, Fu Y et al. 2016. ALKBH1-mediated tRNA demethylation regulates translation. Cell 167:816–28
    [Google Scholar]
  74. 74. 
    Lu Z, Filonov GS, Noto JJ, Schmidt CA, Hatkevich TL et al. 2015. Metazoan tRNA introns generate stable circular RNAs in vivo. RNA 21:1554–65
    [Google Scholar]
  75. 75. 
    Lyons SM, Achorn C, Kedersha NL, Anderson PJ, Ivanov P 2016. YB-1 regulates tiRNA-induced Stress Granule formation but not translational repression. Nucleic Acids Res 44:6949–60
    [Google Scholar]
  76. 76. 
    Lyons SM, Fay MM, Akiyama Y, Anderson PJ, Ivanov P 2017. RNA biology of angiogenin: current state and perspectives. RNA Biol 14:171–78
    [Google Scholar]
  77. 77. 
    Lyons SM, Gudanis D, Coyne SM, Gdaniec Z, Ivanov P 2017. Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs. Nat. Commun. 8:1127
    [Google Scholar]
  78. 78. 
    Martinez A, Yamashita S, Nagaike T, Sakaguchi Y, Suzuki T, Tomita K 2017. Human BCDIN3D monomethylates cytoplasmic histidine transfer RNA. Nucleic Acids Res 45:5423–36
    [Google Scholar]
  79. 79. 
    Masson GR. 2019. Towards a model of GCN2 activation. Biochem. Soc. Trans. 47:1481–88
    [Google Scholar]
  80. 80. 
    Maute RL, Schneider C, Sumazin P, Holmes A, Califano A et al. 2013. tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. PNAS 110:1404–9
    [Google Scholar]
  81. 81. 
    Mefferd AL, Kornepati AV, Bogerd HP, Kennedy EM, Cullen BR 2015. Expression of CRISPR/Cas single guide RNAs using small tRNA promoters. RNA 21:1683–89
    [Google Scholar]
  82. 82. 
    Megel C, Hummel G, Lalande S, Ubrig E, Cognat V et al. 2019. Plant RNases T2, but not Dicer-like proteins, are major players of tRNA-derived fragments biogenesis. Nucleic Acids Res 47:941–52
    [Google Scholar]
  83. 83. 
    Mei Y, Yong J, Liu H, Shi Y, Meinkoth J et al. 2010. tRNA binds to cytochrome c and inhibits caspase activation. Mol. Cell 37:668–78
    [Google Scholar]
  84. 84. 
    Mo D, Jiang P, Yang Y, Mao X, Tan X et al. 2019. A tRNA fragment, 5′-tiRNAVal, suppresses the Wnt/β-catenin signaling pathway by targeting FZD3 in breast cancer. Cancer Lett 457:60–73
    [Google Scholar]
  85. 85. 
    Moutiez M, Belin P, Gondry M 2017. Aminoacyl-tRNA-utilizing enzymes in natural product biosynthesis. Chem. Rev. 117:5578–618
    [Google Scholar]
  86. 86. 
    Noma K, Cam HP, Maraia RJ, Grewal SI 2006. A role for TFIIIC transcription factor complex in genome organization. Cell 125:859–72
    [Google Scholar]
  87. 87. 
    Oberbauer V, Schaefer MR. 2018. tRNA-derived small RNAs: biogenesis, modification, function and potential impact on human disease development. Genes 9:607
    [Google Scholar]
  88. 88. 
    Pan T. 2018. Modifications and functional genomics of human transfer RNA. Cell Res 28:395–404
    [Google Scholar]
  89. 89. 
    Parisien M, Wang X, Pan T 2013. Diversity of human tRNA genes from the 1000-Genomes Project. RNA Biol 10:1853–67
    [Google Scholar]
  90. 90. 
    Parisien M, Wang X, Perdrizet G 2nd, Lamphear C, Fierke CA et al. 2013. Discovering RNA-protein interactome by using chemical context profiling of the RNA-protein interface. Cell Rep 3:1703–13
    [Google Scholar]
  91. 91. 
    Pavon-Eternod M, Gomes S, Geslain R, Dai Q, Rosner MR, Pan T 2009. tRNA over-expression in breast cancer and functional consequences. Nucleic Acids Res 37:7268–80
    [Google Scholar]
  92. 92. 
    Pekarsky Y, Balatti V, Palamarchuk A, Rizzotto L, Veneziano D et al. 2016. Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer. PNAS 113:5071–76
    [Google Scholar]
  93. 93. 
    Phizicky EM, Hopper AK. 2015. tRNA processing, modification, and subcellular dynamics: past, present, and future. RNA 21:483–85
    [Google Scholar]
  94. 94. 
    Pliatsika V, Loher P, Magee R, Telonis AG, Londin E et al. 2018. MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects. Nucleic Acids Res 46:D152–59
    [Google Scholar]
  95. 95. 
    Port F, Bullock SL. 2016. Augmenting CRISPR applications in Drosophila with tRNA-flanked sgRNAs. Nat. Methods 13:852–54
    [Google Scholar]
  96. 96. 
    Raab JR, Chiu J, Zhu J, Katzman S, Kurukuti S et al. 2012. Human tRNA genes function as chromatin insulators. EMBO J 31:330–50
    [Google Scholar]
  97. 97. 
    Reinkemeier CD, Girona GE, Lemke EA 2019. Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes. Science 363:eaaw2644
    [Google Scholar]
  98. 98. 
    Reinsborough CW, Ipas H, Abell NS, Nottingham RM, Yao J et al. 2019. BCDIN3D regulates tRNAHis 3′ fragment processing. PLOS Genet 15:e1008273
    [Google Scholar]
  99. 99. 
    Ren B, Wang X, Duan J, Ma J 2019. Rhizobial tRNA-derived small RNAs are signal molecules regulating plant nodulation. Science 365:919–22
    [Google Scholar]
  100. 100. 
    Ronneau S, Hallez R. 2019. Make and break the alarmone: regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria. FEMS Microbiol. Rev. 43:389–400
    [Google Scholar]
  101. 101. 
    Rudinger-Thirion J, Lescure A, Paulus C, Frugier M 2011. Misfolded human tRNA isodecoder binds and neutralizes a 3′ UTR-embedded Alu element. PNAS 108:E794–802
    [Google Scholar]
  102. 102. 
    Saikia M, Jobava R, Parisien M, Putnam A, Krokowski D et al. 2014. Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress. Mol. Cell. Biol. 34:2450–63
    [Google Scholar]
  103. 103. 
    Sarker G, Sun W, Rosenkranz D, Pelczar P, Opitz L et al. 2019. Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs. PNAS 116:10547–56
    [Google Scholar]
  104. 104. 
    Schaefer M, Pollex T, Hanna K, Tuorto F, Meusburger M et al. 2010. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev 24:1590–95
    [Google Scholar]
  105. 105. 
    Schaffer AE, Eggens VR, Caglayan AO, Reuter MS, Scott E et al. 2014. CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration. Cell 157:651–63
    [Google Scholar]
  106. 106. 
    Schimmel P. 2018. The emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis. Nat. Rev. Mol. Cell Biol. 19:45–58
    [Google Scholar]
  107. 107. 
    Schlee M, Hartmann G. 2016. Discriminating self from non-self in nucleic acid sensing. Nat. Rev. Immunol. 16:566–80
    [Google Scholar]
  108. 108. 
    Schorn AJ, Gutbrod MJ, LeBlanc C, Martienssen R 2017. LTR-retrotransposon control by tRNA-derived small RNAs. Cell 170:61–71.e11
    [Google Scholar]
  109. 109. 
    Schorn AJ, Martienssen R. 2018. Tie-break: host and retrotransposons play tRNA. Trends Cell Biol 28:793–806
    [Google Scholar]
  110. 110. 
    Schwartz MH, Wang H, Pan JN, Clark WC, Cui S et al. 2018. Microbiome characterization by high-throughput transfer RNA sequencing and modification analysis. Nat. Commun. 9:5353
    [Google Scholar]
  111. 111. 
    Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG et al. 2016. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science 351:391–96
    [Google Scholar]
  112. 112. 
    Sheng J, Xu Z. 2016. Three decades of research on angiogenin: a review and perspective. Acta Biochim. Biophys. Sin. 48:399–410
    [Google Scholar]
  113. 113. 
    Shigematsu M, Kawamura T, Kirino Y 2018. Generation of 2′,3′-cyclic phosphate-containing RNAs as a hidden layer of the transcriptome. Front. Genet. 9:562
    [Google Scholar]
  114. 114. 
    Shurtleff MJ, Yao J, Qin Y, Nottingham RM, Temoche-Diaz MM et al. 2017. Broad role for YBX1 in defining the small noncoding RNA composition of exosomes. PNAS 114:E8987–95
    [Google Scholar]
  115. 115. 
    Sobala A, Hutvagner G. 2013. Small RNAs derived from the 5′ end of tRNA can inhibit protein translation in human cells. RNA Biol 10:553–63
    [Google Scholar]
  116. 116. 
    Srinivasan S, Yeri A, Cheah PS, Chung A, Danielson K et al. 2019. Small RNA sequencing across diverse biofluids identifies optimal methods for exRNA isolation. Cell 177:446–62.e16
    [Google Scholar]
  117. 117. 
    Steidinger TU, Standaert DG, Yacoubian TA 2011. A neuroprotective role for angiogenin in models of Parkinson's disease. J. Neurochem. 116:334–41
    [Google Scholar]
  118. 118. 
    Su Z, Frost EL, Lammert CR, Przanowska RK, Lukens JR, Dutta A 2020. tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model. RNA Biol 17:8118395
    [Google Scholar]
  119. 119. 
    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. 294:16930–41
    [Google Scholar]
  120. 120. 
    Tao EW, Cheng WY, Li WL, Yu J, Gao QY 2020. tiRNAs: a novel class of small noncoding RNAs that helps cells respond to stressors and plays roles in cancer progression. J. Cell Physiol. 235:683–90
    [Google Scholar]
  121. 121. 
    Tasaki T, Sriram SM, Park KS, Kwon YT 2012. The N-end rule pathway. Annu. Rev. Biochem. 81:261–89
    [Google Scholar]
  122. 122. 
    Telonis AG, Loher P, Magee R, Pliatsika V, Londin E et al. 2019. tRNA fragments show intertwining with mRNAs of specific repeat content and have links to disparities. Cancer Res 79:3034–49
    [Google Scholar]
  123. 123. 
    Thompson DM, Parker R. 2009. The RNase Rny1p cleaves tRNAs and promotes cell death during oxidative stress in Saccharomyces cerevisiae. J. Cell Biol 185:43–50
    [Google Scholar]
  124. 124. 
    Thompson M, Haeusler RA, Good PD, Engelke DR 2003. Nucleolar clustering of dispersed tRNA genes. Science 302:1399–401
    [Google Scholar]
  125. 125. 
    Thornlow BP, Hough J, Roger JM, Gong H, Lowe TM, Corbett-Detig RB 2018. Transfer RNA genes experience exceptionally elevated mutation rates. PNAS 115:8996–9001
    [Google Scholar]
  126. 126. 
    Torres AG, Reina O, Stephan-Otto Attolini C, Ribas de Pouplana L 2019. Differential expression of human tRNA genes drives the abundance of tRNA-derived fragments. PNAS 116:8451–56
    [Google Scholar]
  127. 127. 
    Tosar JP, Gambaro F, Darre 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 46:9081–93
    [Google Scholar]
  128. 128. 
    Tuorto F, Herbst F, Alerasool N, Bender S, Popp O et al. 2015. The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. EMBO J 34:2350–62
    [Google Scholar]
  129. 129. 
    Tuorto F, Liebers R, Musch T, Schaefer M, Hofmann S et al. 2012. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat. Struct. Mol. Biol. 19:900–5
    [Google Scholar]
  130. 130. 
    Turowski TW, Tollervey D. 2016. Transcription by RNA polymerase III: insights into mechanism and regulation. Biochem. Soc. Trans. 44:1367–75
    [Google Scholar]
  131. 131. 
    Van Bortle K, Corces VG 2012. Nuclear organization and genome function. Annu. Rev. Cell Dev. Biol. 28:163–87
    [Google Scholar]
  132. 132. 
    Van Bortle K, Phanstiel DH, Snyder MP 2017. Topological organization and dynamic regulation of human tRNA genes during macrophage differentiation. Genome Biol 18:180
    [Google Scholar]
  133. 133. 
    van Niel G, D'Angelo G, Raposo G 2018. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19:213–28
    [Google Scholar]
  134. 134. 
    Vitali P, Kiss T. 2019. Cooperative 2′-O-methylation of the wobble cytidine of human elongator tRNAMet(CAT) by a nucleolar and a Cajal body-specific box C/D RNP. Genes Dev 33:741–46
    [Google Scholar]
  135. 135. 
    Wang X, Matuszek Z, Huang Y, Parisien M, Dai Q et al. 2018. Queuosine modification protects cognate tRNAs against ribonuclease cleavage. RNA 24:1305–13
    [Google Scholar]
  136. 136. 
    Weaver JW, Serganov A. 2019. T-box RNA gets boxed. Nat. Struct. Mol. Biol. 26:1081–83
    [Google Scholar]
  137. 137. 
    Wei Y, Qiu Y, Chen Y, Liu G, Zhang Y et al. 2017. CRISPR/Cas9 with single guide RNA expression driven by small tRNA promoters showed reduced editing efficiency compared to a U6 promoter. RNA 23:1–5
    [Google Scholar]
  138. 138. 
    Wei Z, Batagov AO, Schinelli S, Wang J, Wang Y et al. 2017. Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat. Commun. 8:1145
    [Google Scholar]
  139. 139. 
    Xie K, Minkenberg B, Yang Y 2015. Boosting CRISPR/Cas9 multiplex editing capability with the endogenous tRNA-processing system. PNAS 112:3570–75
    [Google Scholar]
  140. 140. 
    Xu L, Zhao L, Gao Y, Xu J, Han R 2017. Empower multiplex cell and tissue-specific CRISPR-mediated gene manipulation with self-cleaving ribozymes and tRNA. Nucleic Acids Res 45:e28
    [Google Scholar]
  141. 141. 
    Yamasaki S, Ivanov P, Hu GF, Anderson P 2009. Angiogenin cleaves tRNA and promotes stress-induced translational repression. J. Cell Biol. 185:35–42
    [Google Scholar]
  142. 142. 
    Yang JY, Deng XY, Li YS, Ma XC, Feng JX et al. 2018. Structure of Schlafen13 reveals a new class of tRNA/rRNA- targeting RNase engaged in translational control. Nat. Commun. 9:1165
    [Google Scholar]
  143. 143. 
    Zhang X, He X, Liu C, Liu J, Hu Q et al. 2016. IL-4 inhibits the biogenesis of an epigenetically suppressive PIWI-interacting RNA to upregulate CD1a molecules on monocytes/dendritic cells. J. Immunol. 196:1591–603
    [Google Scholar]
  144. 144. 
    Zhang X, Lin Y, Eschmann NA, Zhou H, Rauch JN et al. 2017. RNA stores tau reversibly in complex coacervates. PLOS Biol 15:e2002183
    [Google Scholar]
  145. 145. 
    Zhang Y, Wang J, Wang Z, Zhang Y, Shi S et al. 2019. A gRNA-tRNA array for CRISPR-Cas9 based rapid multiplexed genome editing in Saccharomyces cerevisiae. Nat. Commun 10:1053
    [Google Scholar]
  146. 146. 
    Zhang Y, Zhang X, Shi J, Tuorto F, Li X et al. 2018. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nat. Cell Biol. 20:535–40
    [Google Scholar]
  147. 147. 
    Zhang Z, Ruan H, Liu CJ, Ye Y, Gong J et al. 2019. tRic: a user-friendly data portal to explore the expression landscape of tRNAs in human cancers. RNA Biol In press. https://doi.org/10.1080/15476286.2019.1657744
    [Crossref] [Google Scholar]
  148. 148. 
    Zheng LL, Xu WL, Liu S, Sun WJ, Li JH et al. 2016. tRF2Cancer: a web server to detect tRNA-derived small RNA fragments (tRFs) and their expression in multiple cancers. Nucleic Acids Res 44:W185–93
    [Google Scholar]
  149. 149. 
    Zhu B, Lee SJ, Tan M, Wang ED, Richardson CC 2012. Gene 5.5 protein of bacteriophage T7 in complex with Escherichia coli nucleoid protein H-NS and transfer RNA masks transfer RNA priming in T7 DNA replication. PNAS 109:8050–55
    [Google Scholar]
  150. 150. 
    Zhu L, Li J, Gong Y, Wu Q, Tan S et al. 2019. Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis. Mol. Cancer 18:74
    [Google Scholar]
/content/journals/10.1146/annurev-genet-022620-101840
Loading
/content/journals/10.1146/annurev-genet-022620-101840
Loading

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error