1932

Abstract

tRNAs are short noncoding RNAs required for protein translation. The human genome includes more than 600 putative tRNA genes, many of which are considered redundant. tRNA transcripts are subject to tightly controlled, multistep maturation processes that lead to the removal of flanking sequences and the addition of nontemplated nucleotides. Furthermore, tRNAs are highly structured and posttranscriptionally modified. Together, these unique features have impeded the adoption of modern genomics and transcriptomics technologies for tRNA studies. Nevertheless, it has become apparent from human neurogenetic research that many tRNA biogenesis proteins cause brain abnormalities and other neurological disorders when mutated. The cerebral cortex, cerebellum, and peripheral nervous system show defects, impairment, and degeneration upon tRNA misregulation, suggesting that they are particularly sensitive to changes in tRNA expression or function. An integrated approach to identify tRNA species and contextually characterize tRNA function will be imperative to drive future tool development and novel therapeutic design for tRNA-associated disorders.

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2019-08-31
2024-06-23
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Literature Cited

  1. 1.
    Abbasi-Moheb L, Mertel S, Gonsior M, Nouri-Vahid L, Kahrizi K et al. 2012. Mutations in NSUN2 cause autosomal-recessive intellectual disability. Am. J. Hum. Genet. 90:847–55
    [Google Scholar]
  2. 2.
    Alazami AM, Hijazi H, Al-Dosari MS, Shaheen R, Hashem A et al. 2013. Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus. J. Med. Genet. 50:425–30
    [Google Scholar]
  3. 3.
    Alazami AM, Patel N, Shamseldin HE, Anazi S, Al-Dosari MS et al. 2015. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. Cell Rep 10:148–61
    [Google Scholar]
  4. 4.
    Alexandrov A, Chernyakov I, Gu W, Hiley SL, Hughes TR et al. 2006. Rapid tRNA decay can result from lack of nonessential modifications. Mol. Cell 21:87–96
    [Google Scholar]
  5. 5.
    Antonellis A, Ellsworth RE, Sambuughin N, Puls I, Abel A et al. 2003. Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am. J. Hum. Genet. 72:1293–99
    [Google Scholar]
  6. 6.
    Antonellis A, Oprescu SN, Griffin LB, Heider A, Amalfitano A, Innis JW 2018. Compound heterozygosity for loss-of-function FARSB variants in a patient with classic features of recessive aminoacyl-tRNA synthetase-related disease. Hum. Mutat. 39:834–40
    [Google Scholar]
  7. 7.
    Arts GJ, Kuersten S, Romby P, Ehresmann B, Mattaj IW 1998. The role of exportin-t in selective nuclear export of mature tRNAs. EMBO J 17:7430–41
    [Google Scholar]
  8. 8.
    Baer M, Nilsen TW, Costigan C, Altman S 1990. Structure and transcription of a human gene for H1 RNA, the RNA component of human RNase P. Nucleic Acids Res 18:97–103
    [Google Scholar]
  9. 9.
    Bataillard M, Chatzoglou E, Rumbach L, Sternberg D, Tournade A et al. 2001. Atypical MELAS syndrome associated with a new mitochondrial tRNA glutamine point mutation. Neurology 56:405–7
    [Google Scholar]
  10. 10.
    Bayat V, Thiffault I, Jaiswal M, Tetreault M, Donti T et al. 2012. Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans. PLOS Biol 10:e1001288
    [Google Scholar]
  11. 11.
    Beier H, Grimm M. 2001. Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs. Nucleic Acids Res 29:4767–82
    [Google Scholar]
  12. 12.
    Belostotsky R, Ben-Shalom E, Rinat C, Becker-Cohen R, Feinstein S et al. 2011. Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome. Am. J. Hum. Genet. 88:193–200
    [Google Scholar]
  13. 13.
    Bennetzen JL, Hall BD. 1982. Codon selection in yeast. J. Biol. Chem. 257:3026–31
    [Google Scholar]
  14. 14.
    Bernard G, Chouery E, Putorti ML, Tetreault M, Takanohashi A et al. 2011. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am. J. Hum. Genet. 89:415–23
    [Google Scholar]
  15. 15.
    Blakely EL, Trip SA, Swalwell H, He L, Wren DR et al. 2009. A new mitochondrial transfer RNAPro gene mutation associated with myoclonic epilepsy with ragged-red fibers and other neurological features. Arch. Neurol. 66:399–402
    [Google Scholar]
  16. 16.
    Bohm M, Pronicka E, Karczmarewicz E, Pronicki M, Piekutowska-Abramczuk D et al. 2006. Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency. Pediatr. Res. 59:21–26
    [Google Scholar]
  17. 17.
    Bohnsack MT, Czaplinski K, Gorlich D 2004. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10:185–91
    [Google Scholar]
  18. 18.
    Borck G, Hog F, Dentici ML, Tan PL, Sowada N et al. 2015. BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies. Genome Res 25:155–66
    [Google Scholar]
  19. 19.
    Borek E, Baliga BS, Gehrke CW, Kuo CW, Belman S et al. 1977. High turnover rate of transfer RNA in tumor tissue. Cancer Res 37:3362–66
    [Google Scholar]
  20. 20.
    Bovee ML, Yan W, Sproat BS, Francklyn CS 1999. tRNA discrimination at the binding step by a class II aminoacyl-tRNA synthetase. Biochemistry 38:13725–35
    [Google Scholar]
  21. 21.
    Breuss MW, Sultan T, James KN, Rosti RO, Scott E et al. 2016. Autosomal-recessive mutations in the tRNA splicing endonuclease subunit TSEN15 cause pontocerebellar hypoplasia and progressive microcephaly. Am. J. Hum. Genet. 99:228–35
    [Google Scholar]
  22. 22.
    Brzezniak LK, Bijata M, Szczesny RJ, Stepien PP 2011. Involvement of human ELAC2 gene product in 3′ end processing of mitochondrial tRNAs. RNA Biol 8:616–26
    [Google Scholar]
  23. 23.
    Budde BS, Namavar Y, Barth PG, Poll-The BT, Nurnberg G et al. 2008. tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nat. Genet. 40:1113–18
    [Google Scholar]
  24. 24.
    Bykhovskaya Y, Casas K, Mengesha E, Inbal A, Fischel-Ghodsian N 2004. Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). Am. J. Hum. Genet. 74:1303–8
    [Google Scholar]
  25. 25.
    Carter CWJ, Wolfenden R. 2015. tRNA acceptor stem and anticodon bases form independent codes related to protein folding. PNAS 112:7489–94
    [Google Scholar]
  26. 26.
    Chakraborty PK, Schmitz-Abe K, Kennedy EK, Mamady H, Naas T et al. 2014. Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood 124:2867–71
    [Google Scholar]
  27. 27.
    Chan PP, Lowe TM. 2016. GtRNAdb 2.0: an expanded database of transfer RNA genes identified in complete and draft genomes. Nucleic Acids Res 44:D184–89
    [Google Scholar]
  28. 28.
    Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR et al. 2009. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. PNAS 106:19096–101
    [Google Scholar]
  29. 29.
    Ciesla M, Skowronek E, Boguta M 2018. Function of TFIIIC, RNA polymerase III initiation factor, in activation and repression of tRNA gene transcription. Nucleic Acids Res 46:9444–55
    [Google Scholar]
  30. 30.
    Coller JM, Tucker M, Sheth U, Valencia-Sanchez MA, Parker R 2001. The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. RNA 7:1717–27
    [Google Scholar]
  31. 31.
    Copela LA, Fernandez CF, Sherrer RL, Wolin SL 2008. Competition between the Rex1 exonuclease and the La protein affects both Trf4p-mediated RNA quality control and pre-tRNA maturation. RNA 14:1214–27
    [Google Scholar]
  32. 32.
    Cozen AE, Quartley E, Holmes AD, Hrabeta-Robinson E, Phizicky EM, Lowe TM 2015. ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments. Nat. Methods 12:879–84
    [Google Scholar]
  33. 33.
    Dallabona C, Diodato D, Kevelam SH, Haack TB, Wong L-J et al. 2014. Novel (ovario) leukodystrophy related to AARS2 mutations. Neurology 82:2063–71
    [Google Scholar]
  34. 34.
    De Vivo DC, Paradas C, DiMauro S 2014. Mitochondrial encephalomyopathies. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach BT Darras, HR Jones Jr., MM Ryan, DC De Vivo 796–833 Amsterdam: Academic. , 2nd ed..
    [Google Scholar]
  35. 35.
    Deutscher MP. 2006. Degradation of RNA in bacteria: comparison of mRNA and stable RNA. Nucleic Acids Res 34:659–66
    [Google Scholar]
  36. 36.
    Dever TE, Green R. 2012. The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb. Perspect. Biol. 4:a013706
    [Google Scholar]
  37. 37.
    Dhahbi JM, Spindler SR, Atamna H, Yamakawa A, Boffelli D et al. 2013. 5′ tRNA halves are present as abundant complexes in serum, concentrated in blood cells, and modulated by aging and calorie restriction. BMC Genom 14:298
    [Google Scholar]
  38. 38.
    Diodato D, Melchionda L, Haack TB, Dallabona C, Baruffini E et al. 2014. VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies. Hum. Mutat. 35:983–89
    [Google Scholar]
  39. 39.
    Dittmar KA, Goodenbour JM, Pan T 2006. Tissue-specific differences in human transfer RNA expression. PLOS Genet 2:e221
    [Google Scholar]
  40. 40.
    Dixon-Salazar TJ, Silhavy JL, Udpa N, Schroth J, Bielas S et al. 2012. Exome sequencing can improve diagnosis and alter patient management. Sci. Transl. Med. 4:138ra78
    [Google Scholar]
  41. 41.
    Edvardson S, Prunetti L, Arraf A, Haas D, Bacusmo JM et al. 2017. tRNA N6-adenosine threonylcarbamoyltransferase defect due to KAE1/TCS3 (OSGEP) mutation manifest by neurodegeneration and renal tubulopathy. Eur. J. Hum. Genet. 25:545–51
    [Google Scholar]
  42. 42.
    Edvardson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I et al. 2007. Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. Am. J. Hum. Genet. 81:857–62
    [Google Scholar]
  43. 43.
    Eidem TM, Lounsbury N, Emery JF, Bulger J, Smith A et al. 2015. Small-molecule inhibitors of Staphylococcus aureus RnpA-mediated RNA turnover and tRNA processing. Antimicrob. Agents Chemother. 59:2016–28
    [Google Scholar]
  44. 44.
    Ellison JW, Rosenfeld JA, Shaffer LG 2013. Genetic basis of intellectual disability. Annu. Rev. Med. 64:441–50
    [Google Scholar]
  45. 45.
    Evans ME, Clark WC, Zheng G, Pan T 2017. Determination of tRNA aminoacylation levels by high-throughput sequencing. Nucleic Acids Res 45:e133
    [Google Scholar]
  46. 46.
    Feinstein M, Markus B, Noyman I, Shalev H, Flusser H et al. 2010. Pelizaeus-Merzbacher-like disease caused by AIMP1/p43 homozygous mutation. Am. J. Hum. Genet. 87:820–28
    [Google Scholar]
  47. 47.
    Flores A, Briand JF, Gadal O, Andrau JC, Rubbi L et al. 1999. A protein-protein interaction map of yeast RNA polymerase III. PNAS 96:7815–20
    [Google Scholar]
  48. 48.
    Foster PG, Huang L, Santi DV, Stroud RM 2000. The structural basis for tRNA recognition and pseudouridine formation by pseudouridine synthase I. Nat. Struct. Biol. 7:23–27
    [Google Scholar]
  49. 49.
    Fu H, Feng J, Liu Q, Sun F, Tie Y et al. 2009. Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett 583:437–42
    [Google Scholar]
  50. 50.
    Fu H, Hardy J, Duff KE 2018. Selective vulnerability in neurodegenerative diseases. Nat. Neurosci. 21:1350–58
    [Google Scholar]
  51. 51.
    Gamez J, Ferreiro C, Accarino ML, Guarner L, Tadesse S et al. 2002. Phenotypic variability in a Spanish family with MNGIE. Neurology 59:455–57
    [Google Scholar]
  52. 52.
    Ghezzi D, Baruffini E, Haack TB, Invernizzi F, Melchionda L et al. 2012. Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis. Am. J. Hum. Genet. 90:1079–87
    [Google Scholar]
  53. 53.
    Gingold H, Tehler D, Christoffersen NR, Nielsen MM, Asmar F et al. 2014. A dual program for translation regulation in cellular proliferation and differentiation. Cell 158:1281–92
    [Google Scholar]
  54. 54.
    Glover EI, Martin J, Maher A, Thornhill RE, Moran GR, Tarnopolsky MA 2010. A randomized trial of coenzyme Q10 in mitochondrial disorders. Muscle Nerve 42:739–48
    [Google Scholar]
  55. 55.
    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]
  56. 56.
    Gonzalez M, McLaughlin H, Houlden H, Guo M, Yo-Tsen L et al. 2013. Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2. J. Neurol. Neurosurg. Psychiatry 84:1247–49
    [Google Scholar]
  57. 57.
    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]
  58. 58.
    Goto Y, Horai S, Matsuoka T, Koga Y, Nihei K et al. 1992. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation. Neurology 42:545–50
    [Google Scholar]
  59. 59.
    Gotz A, Tyynismaa H, Euro L, Ellonen P, Hyotylainen T et al. 2011. Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy. Am. J. Hum. Genet. 88:635–42
    [Google Scholar]
  60. 60.
    Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J et al. 2013. ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy. Am. J. Hum. Genet. 93:211–23
    [Google Scholar]
  61. 61.
    Hao H, Bonilla E, Manfredi G, DiMauro S, Moraes CT 1995. Segregation patterns of a novel mutation in the mitochondrial tRNA glutamic acid gene associated with myopathy and diabetes mellitus. Am. J. Hum. Genet. 56:1017–25
    [Google Scholar]
  62. 62.
    Hoang C, Ferre-D'Amare AR. 2001. Cocrystal structure of a tRNA Ψ55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Cell 107:929–39
    [Google Scholar]
  63. 63.
    Hoffmann A, Fallmann J, Morl M, Stadler PF, Amman F 2017. Accurate mapping of tRNA reads. Bioinformatics 34:1116–24
    [Google Scholar]
  64. 64.
    Horvath R, Kemp JP, Tuppen HAL, Hudson G, Oldfors A et al. 2009. Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy. Brain Res 132:3165–74
    [Google Scholar]
  65. 65.
    Hu H, Matter ML, Issa-Jahns L, Jijiwa M, Kraemer N et al. 2014. Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness. Ann. Clin. Transl. Neurol. 1:1024–35
    [Google Scholar]
  66. 66.
    Hu W, Sweet TJ, Chamnongpol S, Baker KE, Coller J 2009. Co-translational mRNA decay in Saccharomyces cerevisiae. . Nature 461:225–29
    [Google Scholar]
  67. 67.
    Huang H-Y, Hopper AK. 2015. In vivo biochemical analyses reveal distinct roles of beta-importins and eEF1A in tRNA subcellular traffic. Genes Dev 29:772–83
    [Google Scholar]
  68. 68.
    Huet J, Sentenac A. 1992. The TATA-binding protein participates in TFIIIB assembly on tRNA genes. Nucleic Acids Res 20:6451–54
    [Google Scholar]
  69. 69.
    Intine RV, Sakulich AL, Koduru SB, Huang Y, Pierstorff E et al. 2000. Control of transfer RNA maturation by phosphorylation of the human La antigen on serine 366. Mol. Cell 6:339–48
    [Google Scholar]
  70. 70.
    Ionasescu V, Searby C, Sheffield VC, Roklina T, Nishimura D, Ionasescu R 1996. Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D). Hum. Mol. Genet. 5:1373–75
    [Google Scholar]
  71. 71.
    Ishimura R, Nagy G, Dotu I, Zhou H, Yang XL et al. 2014. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science 345:455–59
    [Google Scholar]
  72. 72.
    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]
  73. 73.
    Jackman JE, Alfonzo JD. 2013. Transfer RNA modifications: nature's combinatorial chemistry playground. WIREs RNA 4:35–48
    [Google Scholar]
  74. 74.
    Jaksch M, Hofmann S, Kleinle S, Liechti-Gallati S, Pongratz DE et al. 1998. A systematic mutation screen of 10 nuclear and 25 mitochondrial candidate genes in 21 patients with cytochrome c oxidase (COX) deficiency shows tRNASer(UCN) mutations in a subgroup with syndromal encephalopathy. J. Med. Genet. 35:895–900
    [Google Scholar]
  75. 75.
    Jarrous N. 2002. Human ribonuclease P: subunits, function, and intranuclear localization. RNA 8:1–7
    [Google Scholar]
  76. 76.
    Jarrous N. 2017. Roles of RNase P and its subunits. Trends Genet 33:594–603
    [Google Scholar]
  77. 77.
    Jordanova A, Thomas FP, Guergueltcheva V, Tournev I, Gondim FAA et al. 2003. Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35. Am. J. Hum. Genet. 73:1423–30
    [Google Scholar]
  78. 78.
    Kadaba S, Krueger A, Trice T, Krecic AM, Hinnebusch AG, Anderson J 2004. Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. . Genes Dev 18:1227–40
    [Google Scholar]
  79. 79.
    Kantidakis T, Ramsbottom BA, Birch JL, Dowding SN, White RJ 2010. mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1. PNAS 107:11823–28
    [Google Scholar]
  80. 80.
    Karaca E, Harel T, Pehlivan D, Jhangiani SN, Gambin T et al. 2015. Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease. Neuron 88:499–513
    [Google Scholar]
  81. 81.
    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]
  82. 82.
    Karnahl U, Wasternack C. 1992. Half-life of cytoplasmic rRNA and tRNA, of plastid rRNA and of uridine nucleotides in heterotrophically and photoorganotrophically grown cells of Euglena gracilis and its apoplastic mutant W3BUL. Int. J. Biochem. 24:493–97
    [Google Scholar]
  83. 83.
    Kessler AC, Silveira d'Almeida G, Alfonzo JD 2018. The role of intracellular compartmentalization on tRNA processing and modification. RNA Biol 15:554–66
    [Google Scholar]
  84. 84.
    Khan MA, Rafiq MA, Noor A, Hussain S, Flores JV et al. 2012. Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. Am. J. Hum. Genet. 90:856–63
    [Google Scholar]
  85. 85.
    Kirchner S, Ignatova Z. 2014. Emerging roles of tRNA in adaptive translation, signalling dynamics and disease. Nat. Rev. Genet. 16:98–112
    [Google Scholar]
  86. 86.
    Kopajtich R, Murayama K, Janecke AR, Haack TB, Breuer M et al. 2016. Biallelic IARS mutations cause growth retardation with prenatal onset, intellectual disability, muscular hypotonia, and infantile hepatopathy. Am. J. Hum. Genet. 99:414–22
    [Google Scholar]
  87. 87.
    Kowalak JA, Pomerantz SC, Crain PF, McCloskey JA 1993. A novel method for the determination of post-transcriptional modification in RNA by mass spectrometry. Nucleic Acids Res 21:4577–85
    [Google Scholar]
  88. 88.
    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]
  89. 89.
    LaCava J, Houseley J, Saveanu C, Petfalski E, Thompson E et al. 2005. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121:713–24
    [Google Scholar]
  90. 90.
    Lareau LF, Hite DH, Hogan GJ, Brown PO 2014. Distinct stages of the translation elongation cycle revealed by sequencing ribosome-protected mRNA fragments. eLife 3:e01257
    [Google Scholar]
  91. 91.
    Latour P, Thauvin-Robinet C, Baudelet-Mery C, Soichot P, Cusin V et al. 2010. A major determinant for binding and aminoacylation of tRNAAla in cytoplasmic alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease. Am. J. Hum. Genet. 86:77–82
    [Google Scholar]
  92. 92.
    Lee M, Park C-H, Chung H-K, Kim HJ, Choi Y et al. 2017. Cerebral white matter abnormalities in patients with Charcot-Marie-Tooth disease. Ann. Neurol. 81:147–51
    [Google Scholar]
  93. 93.
    Lestienne P, Ponsot G. 1988. Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet 331:885
    [Google Scholar]
  94. 94.
    Limongelli A, Schaefer J, Jackson S, Invernizzi F, Kirino Y et al. 2004. Variable penetrance of a familial progressive necrotising encephalopathy due to a novel tRNAIle homoplasmic mutation in the mitochondrial genome. J. Med. Genet. 41:342–49
    [Google Scholar]
  95. 95.
    Lipowsky G, Bischoff FR, Izaurralde E, Kutay U, Schafer S et al. 1999. Coordination of tRNA nuclear export with processing of tRNA. RNA 5:539–49
    [Google Scholar]
  96. 96.
    Liu Y, Satz JS, Vo M-N, Nangle LA, Schimmel P, Ackerman SL 2014. Deficiencies in tRNA synthetase editing activity cause cardioproteinopathy. PNAS 111:17570–75
    [Google Scholar]
  97. 97.
    Lorenz C, Lunse CE, Morl M 2017. tRNA modifications: impact on structure and thermal adaptation. Biomolecules 7:35
    [Google Scholar]
  98. 98.
    Lowe TM, Chan PP. 2016. tRNAscan-SE On-line: integrating search and context for analysis of transfer RNA genes. Nucleic Acids Res 44:W54–57
    [Google Scholar]
  99. 99.
    Machnicka MA, Olchowik A, Grosjean H, Bujnicki JM 2014. Distribution and frequencies of post-transcriptional modifications in tRNAs. RNA Biol 11:1619–29
    [Google Scholar]
  100. 100.
    Maillet L, Collart MA. 2002. Interaction between Not1p, a component of the Ccr4-not complex, a global regulator of transcription, and Dhh1p, a putative RNA helicase. J. Biol. Chem. 277:2835–42
    [Google Scholar]
  101. 101.
    Mancuso M, Filosto M, Mootha VK, Rocchi A, Pistolesi S et al. 2004. A novel mitochondrial tRNAPhe mutation causes MERRF syndrome. Neurology 62:2119–21
    [Google Scholar]
  102. 102.
    McLaughlin HM, Sakaguchi R, Liu C, Igarashi T, Pehlivan D et al. 2010. Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy. Am. J. Hum. Genet. 87:560–66
    [Google Scholar]
  103. 103.
    Melone MAB, Tessa A, Petrini S, Lus G, Sampaolo S et al. 2004. Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERFF phenotype. Arch. Neurol. 61:269–72
    [Google Scholar]
  104. 104.
    Metzger AU, Heckl M, Willbold D, Breitschopf K, RajBhandary UL et al. 1997. Structural studies on tRNA acceptor stem microhelices: exchange of the discriminator base A73 for G in human tRNALeu switches the acceptor specificity from leucine to serine possibly by decreasing the stability of the terminal G1-C72 base pair. Nucleic Acids Res 25:4551–56
    [Google Scholar]
  105. 105.
    Meulemans A, Seneca S, Lagae L, Lissens W, De Paepe B et al. 2006. A novel mitochondrial transfer RNAAsn mutation causing multiorgan failure. Arch. Neurol. 63:1194–98
    [Google Scholar]
  106. 106.
    Mikkelsen NE, Brannvall M, Virtanen A, Kirsebom LA 1999. Inhibition of RNase P RNA cleavage by aminoglycosides. PNAS 96:6155–60
    [Google Scholar]
  107. 107.
    Moqtaderi Z, Wang J, Raha D, White RJ, Snyder M et al. 2010. Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells. Nat. Struct. Mol. Biol. 17:635–40
    [Google Scholar]
  108. 108.
    Morscher RJ, Ducker GS, Li SH-J, Mayer JA, Gitai Z et al. 2018. Mitochondrial translation requires folate-dependent tRNA methylation. Nature 554:128–32
    [Google Scholar]
  109. 109.
    Musante L, Püttmann L, Kahrizi K, Garshasbi M, Hu H et al. 2017. Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability. Hum. Mutat. 38:621–36
    [Google Scholar]
  110. 110.
    Nagaike T, Suzuki T, Tomari Y, Takemoto-Hori C, Negayama F et al. 2001. Identification and characterization of mammalian mitochondrial tRNA nucleotidyltransferases. J. Biol. Chem. 276:40041–49
    [Google Scholar]
  111. 111.
    Nakamura M, Nakano S, Goto Y-I, Ozawa M, Nagahama Y et al. 1995. A novel point mutation in the mitochondrial tRNASer(UCN) gene detected in a family with MERRF/MELAS overlap syndrome. Biochem. Biophys. Res. Commun. 214:86–93
    [Google Scholar]
  112. 112.
    Namavar Y, Barth PG, Poll-The BT, Baas F 2011. Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet. J. Rare Dis. 6:50
    [Google Scholar]
  113. 113.
    Nedialkova DD, Leidel SA. 2015. Optimization of codon translation rates via tRNA modifications maintains proteome integrity. Cell 161:1606–18
    [Google Scholar]
  114. 114.
    Nielsen S, Yuzenkova Y, Zenkin N 2013. Mechanism of eukaryotic RNA polymerase III transcription termination. Science 340:1577–80
    [Google Scholar]
  115. 115.
    Nientiedt M, Deng M, Schmidt D, Perner S, Muller SC, Ellinger J 2016. Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma. Sci. Rep. 6:37158
    [Google Scholar]
  116. 116.
    Nisenbaum C, Sandbank U, Kohn R 1965. Pelizaeusmerzbacher disease “infantile acute type”; report of a family. Ann. Paediatr. 204:365–76
    [Google Scholar]
  117. 117.
    Noren CJ, Anthony-Cahill SJ, Griffith MC, Schultz PG 1989. A general method for site-specific incorporation of unnatural amino acids into proteins. Science 244:182–88
    [Google Scholar]
  118. 118.
    Ozanick SG, Wang X, Costanzo M, Brost RL, Boone C, Anderson JT 2009. Rex1p deficiency leads to accumulation of precursor initiator tRNAMet and polyadenylation of substrate RNAs in Saccharomyces cerevisiae. . Nucleic Acids Res 37:298–308
    [Google Scholar]
  119. 119.
    Ozgur S, Chekulaeva M, Stoecklin G 2010. Human Pat1b connects deadenylation with mRNA decapping and controls the assembly of processing bodies. Mol. Cell. Biol. 30:4308–23
    [Google Scholar]
  120. 120.
    Pan H, Agarwalla S, Moustakas DT, Finer-Moore J, Stroud RM 2003. Structure of tRNA pseudouridine synthase TruB and its RNA complex: RNA recognition through a combination of rigid docking and induced fit. PNAS 100:12648–53
    [Google Scholar]
  121. 121.
    Pang YLJ, Abo R, Levine SS, Dedon PC 2014. Diverse cell stresses induce unique patterns of tRNA up- and down-regulation: tRNA-seq for quantifying changes in tRNA copy number. Nucleic Acids Res 42:e170
    [Google Scholar]
  122. 122.
    Pang YLJ, Poruri K, Martinis SA 2014. tRNA synthetase: tRNA aminoacylation and beyond. WIREs RNA 5:461–80
    [Google Scholar]
  123. 123.
    Paul R, Lazarev D, Altman S 2001. Characterization of RNase P from Thermotoga maritima. . Nucleic Acids Res 29:880–85
    [Google Scholar]
  124. 124.
    Paulson HL, Garbern JY, Hoban TF, Krajewski KM, Lewis RA et al. 2002. Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease. Ann. Neurol. 52:429–34
    [Google Scholar]
  125. 125.
    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]
  126. 126.
    Pelechano V, Wei W, Steinmetz LM 2015. Widespread co-translational RNA decay reveals ribosome dynamics. Cell 161:1400–12
    [Google Scholar]
  127. 127.
    Phizicky EM, Hopper AK. 2010. tRNA biology charges to the front. Genes Dev 24:1832–60
    [Google Scholar]
  128. 128.
    Popow J, Englert M, Weitzer S, Schleiffer A, Mierzwa B et al. 2011. HSPC117 is the essential subunit of a human tRNA splicing ligase complex. Science 331:760–64
    [Google Scholar]
  129. 129.
    Powell CA, Kopajtich R, D'Souza AR, Rorbach J, Kremer LS et al. 2015. TRMT5 mutations cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am. J. Hum. Genet. 97:319–28
    [Google Scholar]
  130. 130.
    Presnyak V, Alhusaini N, Chen Y-H, Martin S, Morris N et al. 2015. Codon optimality is a major determinant of mRNA stability. Cell 160:1111–24
    [Google Scholar]
  131. 131.
    Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA et al. 2012. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLOS ONE 7:e28936
    [Google Scholar]
  132. 132.
    Quax TEF, Claassens NJ, Söll D, van der Oost J 2015. Codon bias as a means to fine-tune gene expression. Mol. Cell 59:149–61
    [Google Scholar]
  133. 133.
    Radhakrishnan A, Chen Y-H, Martin S, Alhusaini N, Green R, Coller J 2016. The DEAD-box protein Dhh1p couples mRNA decay and translation by monitoring codon optimality. Cell 167:122–29
    [Google Scholar]
  134. 134.
    Ramirez A, Shuman S, Schwer B 2008. Human RNA 5′-kinase (hClp1) can function as a tRNA splicing enzyme in vivo. RNA 14:1737–45
    [Google Scholar]
  135. 135.
    Reiter NJ, Osterman A, Torres-Larios A, Swinger KK, Pan T, Mondragon A 2010. Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA. Nature 468:784–89
    [Google Scholar]
  136. 136.
    Riley LG, Rudinger-Thirion J, Schmitz-Abe K, Thorburn DR, Davis RL et al. 2016. LARS2 variants associated with hydrops, lactic acidosis, sideroblastic anemia, and multisystem failure. JIMD Rep 28:49–57
    [Google Scholar]
  137. 137.
    Rodnina MV, Wintermeyer W. 2001. Ribosome fidelity: tRNA discrimination, proofreading and induced fit. Trends Biochem. Sci. 26:124–30
    [Google Scholar]
  138. 138.
    Rogers HH, Griffiths-Jones S. 2014. tRNA anticodon shifts in eukaryotic genomes. RNA 20:269–81
    [Google Scholar]
  139. 139.
    Roovers M, Hale C, Tricot C, Terns MP, Terns RM et al. 2006. Formation of the conserved pseudouridine at position 55 in archaeal tRNA. Nucleic Acids Res 34:4293–301
    [Google Scholar]
  140. 140.
    Ross RL, Cao X, Limbach PA 2017. Mapping post-transcriptional modifications onto transfer ribonucleic acid sequences by liquid chromatography tandem mass spectrometry. Biomolecules 7:21
    [Google Scholar]
  141. 141.
    Rossmanith W. 2011. Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation. PLOS ONE 6:e19152
    [Google Scholar]
  142. 142.
    Rossmanith W, Potuschak T. 2001. Difference between mitochondrial RNase P and nuclear RNase P. Mol. Cell. Biol. 21:8236–37
    [Google Scholar]
  143. 143.
    Rossmanith W, Tullo A, Potuschak T, Karwan R, Sbisa E 1995. Human mitochondrial tRNA processing. J. Biol. Chem. 270:12885–91
    [Google Scholar]
  144. 144.
    Rossor AM, Polke JM, Houlden H, Reilly MM 2013. Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Nat. Rev. Neurol. 9:562–71
    [Google Scholar]
  145. 145.
    Rotig A, Cormier V, Chatelain P, Francois R, Saudubray JM et al. 1993. Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300). J. Clin. Investig. 91:1095–98
    [Google Scholar]
  146. 146.
    Saikia M, Fu Y, Pavon-Eternod M, He C, Pan T 2010. Genome-wide analysis of N1-methyl-adenosine modification in human tRNAs. RNA 16:1317–27
    [Google Scholar]
  147. 147.
    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]
  148. 148.
    Saitsu H, Osaka H, Sasaki M, Takanashi J-I, Hamada K et al. 2011. Mutations in POLR3A and POLR3B encoding RNA polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. Am. J. Hum. Genet. 89:644–51
    [Google Scholar]
  149. 149.
    Santorelli FM, Tanji K, Sano M, Shanske S, El-Shahawi M et al. 1997. Maternally inherited encephalopathy associated with a single-base insertion in the mitochondrial tRNATrp gene. Ann. Neurol. 42:256–60
    [Google Scholar]
  150. 150.
    Schaefer AM, McFarland R, Blakely EL, He L, Whittaker RG et al. 2008. Prevalence of mitochondrial DNA disease in adults. Ann. Neurol. 63:35–39
    [Google Scholar]
  151. 151.
    Schaffer AE, Eggens VRC, 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]
  152. 152.
    Scheper GC, van der Klok T, van Andel RJ, van Berkel CGM, Sissler M et al. 2007. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat. Genet. 39:534–39
    [Google Scholar]
  153. 153.
    Schiffer S, Rosch S, Marchfelder A 2002. Assigning a function to a conserved group of proteins: the tRNA 3′ processing enzymes. EMBO J 21:2769–77
    [Google Scholar]
  154. 154.
    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]
  155. 155.
    Schramm L, Hernandez N. 2002. Recruitment of RNA polymerase III to its target promoters. Genes Dev 16:2593–620
    [Google Scholar]
  156. 156.
    Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J et al. 2011. Global quantification of mammalian gene expression control. Nature 473:337–42
    [Google Scholar]
  157. 157.
    Schwartzentruber J, Buhas D, Majewski J, Sasarman F, Papillon-Cavanagh S et al. 2014. Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome. Hum. Mutat. 35:1285–89
    [Google Scholar]
  158. 158.
    Shah P, Ding Y, Niemczyk M, Kudla G, Plotkin JB 2013. Rate-limiting steps in yeast protein translation. Cell 153:1589–601
    [Google Scholar]
  159. 159.
    Shaheen R, Han L, Faqeih E, Ewida N, Alobeid E et al. 2016. A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition. Hum. Genet. 135:707–13
    [Google Scholar]
  160. 160.
    Shamseldin HE, Alshammari M, Al-Sheddi T, Salih MA, Alkhalidi H et al. 2012. Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes. J. Med. Genet. 49:234–41
    [Google Scholar]
  161. 161.
    Shigematsu M, Honda S, Loher P, Telonis AG, Rigoutsos I, Kirino Y 2017. YAMAT-seq: an efficient method for high-throughput sequencing of mature transfer RNAs. Nucleic Acids Res 5:e70
    [Google Scholar]
  162. 162.
    Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC 1990. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation. Cell 61:931–37
    [Google Scholar]
  163. 163.
    Shukla A, Bhowmik Das A, Hebbar M, Rajagopal KV, Girisha KM et al. 2018. Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis. J. Hum. Genet. 63:19–25
    [Google Scholar]
  164. 164.
    Simons C, Griffin LB, Helman G, Golas G, Pizzino A et al. 2015. Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect. Am. J. Hum. Genet. 96:675–81
    [Google Scholar]
  165. 165.
    Sissler M, Gonzalez-Serrano LE, Westhof E 2017. Recent advances in mitochondrial aminoacyl-tRNA synthetases and disease. Trends Mol. Med. 23:693–708
    [Google Scholar]
  166. 166.
    Sissler M, Helm M, Frugier M, Giege R, Florentz C 2004. Aminoacylation properties of pathology-related human mitochondrial tRNALys variants. RNA 10:841–53
    [Google Scholar]
  167. 167.
    Smith AM, Abu-Shumays R, Akeson M, Bernick DL 2015. Capture, unfolding, and detection of individual tRNA molecules using a nanopore device. Front. Bioeng. Biotechnol. 3:91
    [Google Scholar]
  168. 168.
    Sofou K, Kollberg G, Holmstrom M, Davila M, Darin N et al. 2015. Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome. Mol. Genet. Genom. Med. 3:59–68
    [Google Scholar]
  169. 169.
    Solivio B, Yu N, Addepalli B, Limbach PA 2018. Improving RNA modification mapping sequence coverage by LC-MS through a nonspecific RNase U2-E49A mutant. Anal. Chim. Acta 1036:73–79
    [Google Scholar]
  170. 170.
    Steenweg ME, Ghezzi D, Haack T, Abbink TEM, Martinelli D et al. 2012. Leukoencephalopathy with thalamus and brainstem involvement and high lactate ‘LTBL’ caused by EARS2 mutations. Brain Res 135:1387–94
    [Google Scholar]
  171. 171.
    Suzuki T, Nagao A, Suzuki T 2011. Human mitochondrial tRNAs: biogenesis, function, structural aspects, and diseases. Annu. Rev. Genet. 45:299–329
    [Google Scholar]
  172. 172.
    Swalwell H, Kirby DM, Blakely EL, Mitchell A, Salemi R et al. 2011. Respiratory chain complex I deficiency caused by mitochondrial DNA mutations. Eur. J. Hum. Genet. 19:769–75
    [Google Scholar]
  173. 173.
    Taft RJ, Vanderver A, Leventer RJ, Damiani SA, Simons C et al. 2013. Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity. Am. J. Hum. Genet. 92:774–80
    [Google Scholar]
  174. 174.
    Takaku H, Minagawa A, Takagi M, Nashimoto M 2003. A candidate prostate cancer susceptibility gene encodes tRNA 3′ processing endoribonuclease. Nucleic Acids Res 31:2272–78
    [Google Scholar]
  175. 175.
    Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J et al. 2014. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA 312:68–77
    [Google Scholar]
  176. 176.
    Taylor RW, Taylor GA, Durham SE, Turnbull DM 2001. The determination of complete human mitochondrial DNA sequences in single cells: implications for the study of somatic mitochondrial DNA point mutations. Nucleic Acids Res 29:E74
    [Google Scholar]
  177. 177.
    Thompson DM, Lu C, Green PJ, Parker R 2008. tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA 14:2095–103
    [Google Scholar]
  178. 178.
    Torres AG, Pineyro D, Rodriguez-Escriba M, Camacho N, Reina O et al. 2015. Inosine modifications in human tRNAs are incorporated at the precursor tRNA level. Nucleic Acids Res 43:5145–57
    [Google Scholar]
  179. 179.
    Trotta CR, Miao F, Arn EA, Stevens SW, Ho CK et al. 1997. The yeast tRNA splicing endonuclease: a tetrameric enzyme with two active site subunits homologous to the archaeal tRNA endonucleases. Cell 89:849–58
    [Google Scholar]
  180. 180.
    Tucker EJ, Hershman SG, Kohrer C, Belcher-Timme CA, Patel J et al. 2011. Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab 14:428–34
    [Google Scholar]
  181. 181.
    Tuller T, Carmi A, Vestsigian K, Navon S, Dorfan Y et al. 2010. An evolutionarily conserved mechanism for controlling the efficiency of protein translation. Cell 141:344–54
    [Google Scholar]
  182. 182.
    Urbonavicius J, Qian Q, Durand JM, Hagervall TG, Bjork GR 2001. Improvement of reading frame maintenance is a common function for several tRNA modifications. EMBO J 20:4863–73
    [Google Scholar]
  183. 183.
    Urbonavicius J, Stahl G, Durand JMB, Ben Salem SN, Qian Q et al. 2003. Transfer RNA modifications that alter +1 frameshifting in general fail to affect −1 frameshifting. RNA 9:760–68
    [Google Scholar]
  184. 184.
    Veerapandiyan A, Chaudhari A, Traba CM, Ming X 2016. Novel mutation in mitochondrial DNA in 2 siblings with Leigh syndrome. Neurol Genet 2:e99
    [Google Scholar]
  185. 185.
    Vernon HJ, McClellan R, Batista DAS, Naidu S 2015. Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings. Am. J. Med. Genet. A 167A:1147–51
    [Google Scholar]
  186. 186.
    Vester A, Velez-Ruiz G, McLaughlin HM, Lupski JR, Talbot K et al. 2013. A loss-of-function variant in the human histidyl-tRNA synthetase (HARS) gene is neurotoxic in vivo. Hum. Mutat. 34:191–99
    [Google Scholar]
  187. 187.
    Vilarinho L, Santorelli FM, Rosas MJ, Tavares C, Melo-Pires M, DiMauro S 1997. The mitochondrial A3243G mutation presenting as severe cardiomyopathy. J. Med. Genet. 34:607–9
    [Google Scholar]
  188. 188.
    Vorlander MK, Khatter H, Wetzel R, Hagen WJH, Muller CW 2018. Molecular mechanism of promoter opening by RNA polymerase III. Nature 553:295–300
    [Google Scholar]
  189. 189.
    Walker SC, Engelke DR. 2008. A protein-only RNase P in human mitochondria. Cell 135:412–14
    [Google Scholar]
  190. 190.
    Wang M, Zhu Y, Wang C, Fan X, Jiang X et al. 2016. Crystal structure of the two-subunit tRNA m1A58 methyltransferase TRM6-TRM61 from Saccharomyces cerevisiae. Sci. Rep 6:32562
    [Google Scholar]
  191. 191.
    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]
  192. 192.
    Webb BD, Wheeler PG, Hagen JJ, Cohen N, Linderman MD et al. 2015. Novel, compound heterozygous, single-nucleotide variants in MARS2 associated with developmental delay, poor growth, and sensorineural hearing loss. Hum. Mutat. 36:587–92
    [Google Scholar]
  193. 193.
    Webster MW, Chen Y-H, Stowell JAW, Alhusaini N, Sweet T et al. 2018. mRNA deadenylation is coupled to translation rates by the differential activities of Ccr4–Not nucleases. Mol. Cell 70:1089–100.e8
    [Google Scholar]
  194. 194.
    Whipple JM, Lane EA, Chernyakov I, D'Silva S, Phizicky EM 2011. The yeast rapid tRNA decay pathway primarily monitors the structural integrity of the acceptor and T-stems of mature tRNA. Genes Dev 25:1173–84
    [Google Scholar]
  195. 195.
    White RJ, Gottlieb TM, Downes CS, Jackson SP 1995. Cell cycle regulation of RNA polymerase III transcription. Mol. Cell. Biol. 15:6653–62
    [Google Scholar]
  196. 196.
    Wilusz JE, Whipple JM, Phizicky EM, Sharp PA 2011. tRNAs marked with CCACCA are targeted for degradation. Science 334:817–21
    [Google Scholar]
  197. 197.
    Wolf NI, Salomons GS, Rodenburg RJ, Pouwels PJW, Schieving JH et al. 2014. Mutations in RARS cause hypomyelination. Ann. Neurol. 76:134–39
    [Google Scholar]
  198. 198.
    Wolin SL, Matera AG. 1999. The trials and travels of tRNA. Genes Dev 13:1–10
    [Google Scholar]
  199. 199.
    Yacoubi El B, Bailly M, de Crecy-Lagard V 2012. Biosynthesis and function of posttranscriptional modifications of transfer RNAs. Annu. Rev. Genet. 46:69–95
    [Google Scholar]
  200. 200.
    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]
  201. 201.
    Yarham JW, Lamichhane TN, Pyle A, Mattijssen S, Baruffini E et al. 2014. Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA. PLOS Genet 10:e1004424
    [Google Scholar]
  202. 202.
    Yeri A, Courtright A, Reiman R, Carlson E, Beecroft T et al. 2017. Total extracellular small RNA profiles from plasma, saliva, and urine of healthy subjects. Sci. Rep. 7:44061
    [Google Scholar]
  203. 203.
    Yi H, Park J, Ha M, Lim J, Chang H, Kim VN 2018. PABP cooperates with the CCR4-NOT complex to promote mRNA deadenylation and block precocious decay. Mol. Cell 70:1081–85
    [Google Scholar]
  204. 204.
    Yoo CJ, Wolin SL. 1997. The yeast La protein is required for the 3′ endonucleolytic cleavage that matures tRNA precursors. Cell 89:393–402
    [Google Scholar]
  205. 205.
    Yoon KL, Aprille JR, Ernst SG 1991. Mitochondrial tRNAthr mutation in fatal infantile respiratory enzyme deficiency. Biochem. Biophys. Res. Commun. 176:1112–15
    [Google Scholar]
  206. 206.
    Yoshihisa T, Yunoki-Esaki K, Ohshima C, Tanaka N, Endo T 2003. Possibility of cytoplasmic pre-tRNA splicing: the yeast tRNA splicing endonuclease mainly localizes on the mitochondria. Mol. Biol. Cell 14:3266–79
    [Google Scholar]
  207. 207.
    Zeviani M, Muntoni F, Savarese N, Serra G, Tiranti V et al. 1993. A MERRF/MELAS overlap syndrome associated with a new point mutation in the mitochondrial DNA tRNALys gene. Eur. J. Hum. Genet. 1:80–87
    [Google Scholar]
  208. 208.
    Zhang X, Cozen AE, Liu Y, Chen Q, Lowe TM 2016. Small RNA modifications: integral to function and disease. Trends Mol. Med. 22:1025–34
    [Google Scholar]
  209. 209.
    Zhang X, Ling J, Barcia G, Jing L, Wu J et al. 2014. Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. Am. J. Hum. Genet. 94:547–58
    [Google Scholar]
  210. 210.
    Zheng G, Qin Y, Clark WC, Dai Q, Yi C et al. 2015. Efficient and quantitative high-throughput tRNA sequencing. Nat. Methods 12:835–37
    [Google Scholar]
  211. 211.
    Zouridis H, Hatzimanikatis V. 2008. Effects of codon distributions and tRNA competition on protein translation. Biophys. J. 95:1018–33
    [Google Scholar]
  212. 212.
    Zschocke J, Ruiter JP, Brand J, Lindner M, Hoffmann GF et al. 2000. Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched-chain fatty acid and isoleucine metabolism. Pediatr. Res. 48:852–55
    [Google Scholar]
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