1932

Abstract

Enzymes that phosphorylate, dephosphorylate, and ligate RNA 5′ and 3′ ends were discovered more than half a century ago and were eventually shown to repair purposeful site-specific endonucleolytic breaks in the RNA phosphodiester backbone. The pace of discovery and characterization of new candidate RNA repair activities in taxa from all phylogenetic domains greatly exceeds our understanding of the biological pathways in which they act. The key questions anent RNA break repair in vivo are () identifying the triggers, agents, and targets of RNA cleavage and () determining whether RNA repair results in restoration of the original RNA, modification of the RNA (by loss or gain at the ends), or rearrangements of the broken RNA segments (i.e., RNA recombination). This review provides a perspective on the discovery, mechanisms, and physiology of purposeful RNA break repair, highlighting exemplary repair pathways (e.g., tRNA restriction-repair and tRNA splicing) for which genetics has figured prominently in their elucidation.

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2023-11-27
2024-04-15
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Literature Cited

  1. 1.
    Amitsur M, Levitz R, Kaufmann G. 1987. Bacteriophage T4 anticodon nuclease, polynucleotide kinase and RNA ligase reprocess the host lysine tRNA. EMBO J. 6:2499–503
    [Google Scholar]
  2. 2.
    Aphasizheva I, Aphasizhev R. 2016. U-insertion/deletion mRNA-editing holoenzyme: definition in sight. Trends Parasitol. 32:144–56
    [Google Scholar]
  3. 3.
    Asanović I, Strandback E, Kroupova A, Pasajlic D, Meinhart A et al. 2021. The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response. Mol. Cell 81:2520–32
    [Google Scholar]
  4. 4.
    Banerjee A, Ghosh S, Goldgur Y, Shuman S. 2019. Structure and two-metal mechanism of fungal tRNA ligase. Nucleic Acids Res. 47:1428–39
    [Google Scholar]
  5. 5.
    Banerjee A, Goldgur Y, Schwer B, Shuman S. 2019. Atomic structures of the RNA end-healing 5′-OH kinase and 2′,3′-cyclic phosphodiesterase domains of fungal tRNA ligase: conformational switches in the kinase upon binding of the GTP phosphate donor. Nucleic Acids Res. 47:11826–38
    [Google Scholar]
  6. 6.
    Banerjee A, Goldgur Y, Shuman S. 2021. Structure of 3′-PO4/5′-OH RNA ligase RtcB in complex with a 5′-OH oligonucleotide. RNA 27:584–90
    [Google Scholar]
  7. 7.
    Banerjee A, Munir A, Abdullahu L, Damha MJ, Goldgur Y, Shuman S. 2019. Structure of tRNA splicing enzyme Tpt1 illuminates the mechanism of RNA 2′-PO4 recognition and ADP-ribosylation. Nat. Comm. 10:218
    [Google Scholar]
  8. 8.
    Blanga-Kanfi S, Amitsur M, Azem A, Kaufmann G. 2006. PrrC-anticodon nuclease: functional organization of a prototypical bacteria restriction RNase. Nucleic Acids Res. 34:3209–19
    [Google Scholar]
  9. 9.
    Burroughs AM, Aravind L. 2016. RNA damage in biological conflicts and the diversity of responding RNA repair systems. Nucleic Acids Res. 44:8525–55
    [Google Scholar]
  10. 10.
    Chakravarty AK, Shuman S. 2012. The sequential 2′,3′ cyclic phosphodiesterase and 3′-phosphate/5′-OH ligation steps of the RtcB RNA splicing pathway are GTP-dependent. Nucleic Acids Res. 40:8558–67
    [Google Scholar]
  11. 11.
    Chakravarty AK, Subbotin R, Chait BT, Shuman S. 2012. RNA ligase RtcB splices 3′-phosphate and 5′-OH ends via covalent RtcB-(histidinyl)-GMP and polynucleotide-(3′)pp(5′)G intermediates. PNAS 109:6072–77
    [Google Scholar]
  12. 12.
    Chan CM, Zhou C, Brunzelle JS, Huang RH. 2009. Structural and biochemical insights into 2′-O-methylation at the 3′-terminal nucleotide of RNA by Hen1. PNAS 106:17699–704
    [Google Scholar]
  13. 13.
    Chan CM, Zhou C, Huang R. 2009. Reconstituting bacterial RNA repair and modification in vitro. Science 326:247
    [Google Scholar]
  14. 14.
    Chen X, Wolin SL. 2023. Transfer RNA halves are found as nicked tRNAs in cells: evidence that nicked tRNAs regulate expression of an RNA repair operon. RNA 29:620–29
    [Google Scholar]
  15. 15.
    Costa B, Calzi ML, Castellano M, Blanco V, Cuevasanta E et al. 2023. Nicked tRNAs are stable reservoirs of tRNA halves in cell and biofluids. PNAS 120:e2216330120
    [Google Scholar]
  16. 16.
    Culver GM, McCraith SM, Consaul SA, Stanford DR, Phizicky EM. 1997. A 2′-phosphotransferase implicated in tRNA splicing is essential in Saccharomyces cerevisiae. J. Biol. Chem. 272:13203–10
    [Google Scholar]
  17. 17.
    Culver GM, McCraith SM, Zillman M, Kierzek R, Michaud N et al. 1993. An NAD derivative produced during transfer RNA splicing: ADP-ribose 1′′-2′′ cyclic phosphate. Science 261:206–8
    [Google Scholar]
  18. 18.
    Dantuluri S, Abdullahu L, Munir A, Katolik A, Damha MJ, Shuman S. 2020. Substrate analogs that trap the 2′-phospho-ADP-ribosylated RNA intermediate of the Tpt1 (tRNA 2′-phosphotransferase) reaction pathway. RNA 26:373–81
    [Google Scholar]
  19. 19.
    Dantuluri S, Schwer B, Abdullahu L, Damha MJ, Shuman S. 2021. Activity and substrate specificity of Candida, Aspergillus, and Coccidioides Tpt1: essential tRNA splicing enzymes and potential antifungal targets. RNA 27:616–27
    [Google Scholar]
  20. 20.
    Das U, Chakravarty AK, Remus BS, Shuman S. 2013. Rewriting the rules for end joining via enzymatic splicing of DNA 3′-PO4 and 5′-OH ends. PNAS 110:20437–42
    [Google Scholar]
  21. 21.
    Das U, Shuman S. 2013. Mechanism of RNA 2′,3′-cyclic phosphate end healing by T4 polynucleotide kinase–phosphatase. Nucleic Acids Res. 41:355–65
    [Google Scholar]
  22. 22.
    Das U, Wang LK, Smith P, Jacewicz A, Shuman S. 2014. Structures of bacterial polynucleotide kinase in a Michaelis complex with GTP · Mg2+ and 5′-OH oligonucleotide and a product complex with GDP · Mg2+ and 5′-PO4 oligonucleotide reveal a mechanism of general acid-base catalysis and the determinants of phosphoacceptor recognition. Nucleic Acids Res. 42:1152–61
    [Google Scholar]
  23. 23.
    David M, Borasio GD, Kaufmann G. 1982. Bacteriophage T4-induced anticodon-loop nuclease detected in a host strain restrictive to RNA ligase mutants. PNAS 79:7097–101
    [Google Scholar]
  24. 24.
    Depew RE, Cozzarelli NR. 1974. Genetics and physiology of bacteriophage T4 3′-phosphatase: evidence for involvement of the enzyme in T4 DNA metabolism. J. Virol. 13:888–97
    [Google Scholar]
  25. 25.
    Desai KK, Beltrame AL, Raines RT. 2015. Coevolution of RtcB and Archease created a multiple-turnover RNA ligase. RNA 21:1866–72
    [Google Scholar]
  26. 26.
    Desai KK, Bingman CA, Phillips GN, Raines RT. 2013. Structures of the noncanonical RNA ligase RtcB reveal the mechanism of histidine guanylylation. Biochemistry 52:2518–25
    [Google Scholar]
  27. 27.
    Desai KK, Cheng CL, Bingman CA, Phillips GN, Raines RT. 2014. A tRNA splicing operon: archease endows RtcB with dual GTP/ATP cofactor specificity and accelerates RNA ligation. Nucleic Acids Res. 42:3931–42
    [Google Scholar]
  28. 28.
    Durantel D, Croizier L, Ayres MD, Croizier G, Possee RD, Lopez-Ferber M. 1998. The pnk/pnl gene (ORF86) of Autographa californica nucleopolyhedrovirus is a non-essential, immediate early gene. J. Gen. Virol. 79:629–37
    [Google Scholar]
  29. 29.
    Eastberg JH, Pelletier J, Stoddard BL. 2004. Recognition of DNA substrates by bacteriophage T4 polynucleotide kinase. Nucleic Acids Res. 32:653–60
    [Google Scholar]
  30. 30.
    El Omari K, Ren J, Bird LE, Bona MK, Klarmann G et al. 2005. Molecular architecture and ligand recognition determinants for T4 RNA ligase. J. Biol. Chem. 281:1573–79
    [Google Scholar]
  31. 31.
    Engl C, Schaefer J, Kotta-Loizou I, Buck M. 2016. Cellular and molecular phenotypes depending upon the RNA repair system RtcAB of Escherichia coli. Nucleic Acids Res. 44:9933–41
    [Google Scholar]
  32. 32.
    Englert M, Beier H. 2005. Plant tRNA ligases are multifunctional enzymes that have diverged in sequence and substrate specificity from RNA ligases of other phylogenetic origins. Nucleic Acids Res. 33:388–99
    [Google Scholar]
  33. 33.
    Englert M, Sheppard K, Aslanian A, Yates JR III, Söll D 2011. Archaeal 3′-phosphate RNA splicing ligase characterization identifies the missing component in tRNA maturation. PNAS 108:1290–95
    [Google Scholar]
  34. 34.
    Englert M, Sheppard K, Gundllapalli S, Beier H, Söll D. 2010. Branchiostoma floridae has separate healing and sealing enzymes for 5′-phosphate RNA ligation. PNAS 107:16834–39
    [Google Scholar]
  35. 35.
    Englert M, Xia S, Okada C, Nakamura A, Tanavde V et al. 2012. Structural and mechanistic insights into guanylylation of RNA-splicing ligase RtcB joining between 3′-terminal phosphate and 5′-OH. PNAS 109:15235–40
    [Google Scholar]
  36. 36.
    Filipowicz W, Shatkin AJ. 1983. Origin of splice junction phosphate in tRNAs processed by HeLa cell extract. Cell 32:547–57
    [Google Scholar]
  37. 37.
    Galburt EA, Pelletier J, Wilson G, Stoddard BL. 2002. Structure of a tRNA repair enzyme and molecular biology workhorse: T4 polynucleotide kinase. Structure 10:1249–60
    [Google Scholar]
  38. 38.
    Gegenheimer P, Gabius HJ, Peebles CL, Abelson J. 1983. An RNA ligase from wheat germ which participates in transfer RNA splicing in vitro. J. Biol. Chem. 258:8365–73
    [Google Scholar]
  39. 39.
    Genschik P, Drabikowski K, Filipowicz W. 1998. Characterization of the Escherichia coli RNA 3′-terminal phosphate cyclase and its σ54-regulated operon. J. Biol. Chem. 273:25516–26
    [Google Scholar]
  40. 40.
    Gerber JL, Köhler S, Peschek J. 2022. Eukaryotic tRNA splicing—one goal, two strategies, many players. Biol. Chem. 403:765–78
    [Google Scholar]
  41. 41.
    Gerber JL, Guzmán SIM, Worf L, Hubbe P, Kopp J, Peschek J. 2023. Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease. bioRxiv 2023.03.30.534986. https://doi.org/10.1101/2023.03.30.534986
  42. 42.
    Gonzalez TN, Sidrauski C, Dörfler S, Walter P. 1999. Mechanism of non-spliceosomal mRNA splicing in the unfolded protein response pathway. EMBO J. 18:3119–32
    [Google Scholar]
  43. 43.
    Greer CL, Peebles CL, Gegenheimer P, Abelson J. 1983. Mechanism of action of a yeast RNA ligase in tRNA splicing. Cell 32:537–46
    [Google Scholar]
  44. 44.
    Harding HP, Lackey JG, Hsu H-C, Zhang Y, Deng J et al. 2008. An intact unfolded protein response in Trpt1 knockout mice reveals phylogenic divergence in pathways for RNA ligation. RNA 14:225–32
    [Google Scholar]
  45. 45.
    Ho CK, Shuman S. 2002. Bacteriophage T4 RNA ligase 2 (gp24.1) exemplifies a family of RNA ligases found in all phylogenetic domains. PNAS 99:12709–14
    [Google Scholar]
  46. 46.
    Hughes KJ, Chen X, Burroughs AM, Aravind L, Wolin SL. 2020. An RNA repair operon regulated by damaged tRNAs. Cell Rep. 33:108527
    [Google Scholar]
  47. 47.
    Jabbar MA, Snyder L. 1984. Genetic and physiological studies of an Escherichia coli locus that restricts polynucleotide kinase- and RNA ligase-deficient mutants of bacteriophage T4. J. Virol. 51:522–29
    [Google Scholar]
  48. 48.
    Jacewicz A, Dantuluri S, Shuman S. 2022. Structures of RNA ligase RtcB in complexes with divalent cations and GTP. RNA 28:1509–18
    [Google Scholar]
  49. 49.
    Jain R, Shuman S. 2010. Bacterial Hen1 is a 3′ terminal RNA ribose 2′-O-methyltransferase component of a bacterial RNA repair cassette. RNA 16:316–23
    [Google Scholar]
  50. 50.
    Jain R, Shuman S. 2011. Active site mapping and substrate specificity of bacterial Hen1, a manganese-dependent 3′ terminal RNA ribose 2′O-methyltransferase. RNA 17:429–38
    [Google Scholar]
  51. 51.
    Jurkin J, Henkel T, Nielsen AF, Minnich M, Popow J et al. 2014. The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells. EMBO J. 33:2922–36
    [Google Scholar]
  52. 52.
    Kaufmann G, David M, Borasio GD, Teichmann A, Paz A, Amitsur M. 1986. Phage and host genetic determinants of the specific anticodon loop cleavages in bacteriophage T4-infected Escherichia coli CTr5X. . J. Mol. Biol. 188:15–22
    [Google Scholar]
  53. 53.
    Keppetipola N, Shuman S. 2006. Mechanism of the phosphatase component of Clostridium thermocellum polynucleotide kinase-phosphatase. RNA 12:73–82
    [Google Scholar]
  54. 54.
    Knapp G, Beckmann JS, Johnson PF, Fuhrman SA, Abelson J. 1978. Transcription and processing of intervening sequences in yeast tRNA genes. Cell 14:221–36
    [Google Scholar]
  55. 55.
    Konarska M, Filipowicz W, Domdey H, Gross HJ. 1981. Formation of a 2′-phosphomonoester, 3′,5′-phosphodiester linkage by a novel RNA ligase in wheat germ. Nature 293:112–16
    [Google Scholar]
  56. 56.
    Konarska M, Filipowicz W, Gross HJ. 1982. RNA ligation via 2′-phosphomonoester, 3′5′-phosphodiester linkage: requirement of 2′,3′-cyclic phosphate termini and involvement of a 5′-hydroxyl polynucleotide kinase. PNAS 79:1474–78
    [Google Scholar]
  57. 57.
    Kosmaczewski SG, Edwards TJ, Han SM, Eckwahl MJ, Meyer BI et al. 2014. The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO Rep. 15:1278–85
    [Google Scholar]
  58. 58.
    Kroupova A, Ackle F, Asanovic I, Weitzer S, Boneberg FM et al. 2021. Molecular architecture of the human tRNA ligase complex. eLife 10:e71656
    [Google Scholar]
  59. 59.
    Krutkina E, Klaiman D, Margalit T, Jerabeck-Willemsen M, Kaufmann G. 2016. Dual nucleotide specificity determinants of an infection aborting anticodon nuclease. Virology 487:260–72
    [Google Scholar]
  60. 60.
    Kurasz JE, Hartman CE, Samuels DJ, Mohanty BK, Deleveaux A et al. 2018. Genotoxic, metabolic, and oxidative stresses regulate the RNA repair operon of Salmonella enterica serovar Typhimurium. J. Bacteriol. 200:e00476-18
    [Google Scholar]
  61. 61.
    Laski FA, Fire AZ, RajBhandary UL, Sharp PA. 1983. Characterization of tRNA precursor splicing in mammalian extracts. J. Biol. Chem. 258:11974–80
    [Google Scholar]
  62. 62.
    Li H, Trotta CR, Abelson J. 1998. Crystal structure and evolution of a transfer RNA splicing enzyme. Science 280:279–84
    [Google Scholar]
  63. 63.
    Loeff L, Kroupova A, Asanović I, Boneberg F, Pfleiderer M et al. 2023. Mechanistic basis for oxidative stress protection of the human tRNA ligase complex by the oxidoreductase PYROXD1. bioRxiv 2023.04.06.535761. https://doi.org/10.1101/2023.04.06.535761
  64. 64.
    Lopes RR, Silveira G, Eitler R, Vidal RS, Kessler A et al. 2016. The essential function of the Trypanosoma brucei Trl1 homolog in procyclic cells is maturation of the intron-containing tRNATyr. RNA 22:1190–99
    [Google Scholar]
  65. 65.
    Lopez VA, Hu Y, Pawlowski K, Tagliabracci VS. 2022. Discovery of a human 5′ to 3′ RNA ligase Abstract from the 27th Annual RNA Society Meeting Boulder, CO:
  66. 66.
    Lu Y, Liang FX, Wang X. 2014. A synthetic biology approach identifies the mammalian UPR RNA ligase RtcB. Mol. Cell 55:758–70
    [Google Scholar]
  67. 67.
    Magee R, Rigoutsos I. 2020. On the expanding roles of tRNA fragments in modulating cell behavior. Nucleic Acids Res. 48:9433–88
    [Google Scholar]
  68. 68.
    Makarova KS, Timinskas A, Wolf YI, Gussow AB, Siksnys V et al. 2020. Evolutionary and functional classification of the CARF domain superfamily, key sensors in prokaryotic antivirus defense. Nucleic Acids Res. 48:8828–47
    [Google Scholar]
  69. 69.
    Martins A, Shuman S. 2004. Characterization of a baculovirus enzyme with RNA ligase, polynucleotide 5′-kinase, and polynucleotide 3′-phosphatase activities. J. Biol. Chem. 279:18220–31
    [Google Scholar]
  70. 70.
    Martins A, Shuman S. 2005. An end-healing enzyme from Clostridium thermocellum with 5′ kinase, 2′,3′ phosphatase, and adenylyltransferase activities. RNA 11:1271–80
    [Google Scholar]
  71. 71.
    Maughan WP, Shuman S. 2015. Characterization of 3′-phosphate RNA ligase paralogs RtcB1, RtcB2, and RtcB3 from Myxococcus xanthus highlights DNA and RNA 5′-phosphate capping activity of RtcB3. J. Bacteriol. 197:3616–24
    [Google Scholar]
  72. 72.
    Maughan WP, Shuman S. 2016. Distinct contributions of enzymic functional groups to the 2′,3′-cyclic phosphodiesterase, 3′-phosphate guanylylation, and 3′-ppG/5′-OH ligation steps of the Escherichia coli RtcB nucleic acid splicing pathway. J. Bacteriol. 198:1294–304
    [Google Scholar]
  73. 73.
    McCraith SM, Phizicky EM. 1990. A highly specific phosphatase from Saccharomyces cerevisiae implicated in tRNA splicing. Mol. Cell. Biol. 10:1049–55
    [Google Scholar]
  74. 74.
    McCraith SM, Phizicky EM. 1991. An enzyme from Saccharomyces cerevisiae uses NAD+ to transfer the splice junction 2′-phosphate from ligated tRNA to an acceptor molecule. J. Biol. Chem. 266:11986–92
    [Google Scholar]
  75. 75.
    Meineke B, Schwer B, Schaffrath R, Shuman S. 2011. Determinants of eukaryal cell killing by the bacterial ribotoxin PrrC. Nucleic Acids Res. 39:687–700
    [Google Scholar]
  76. 76.
    Meineke B, Shuman S. 2012. Structure–function relations in the NTPase domain of the antiviral tRNA ribotoxin Escherichia coli PrrC. Virology 427:144–50
    [Google Scholar]
  77. 77.
    Mori T, Ogasawara C, Inada T, Englert M, Beier H et al. 2010. Dual functions of yeast tRNA ligase in the unfolded protein response: Unconventional cytoplasmic splicing of HAC1 pre-mRNA is not sufficient to release translational attenuation. Mol. Biol. Cell 21:3722–34
    [Google Scholar]
  78. 78.
    Munir A, Abdullahu L, Damha MJ, Shuman S. 2018. Two-step mechanism and step-arrest mutants of Runella slithyformis NAD+-dependent tRNA 2′-phosphotransferase Tpt1. RNA 24:1144–57
    [Google Scholar]
  79. 79.
    Munir A, Banerjee A, Shuman S. 2018. NAD+-dependent synthesis of a 5′-phospho-ADP-ribosylated RNA/DNA cap by RNA 2′-phosphotransferase Tpt1. Nucleic Acids Res. 46:9617–24
    [Google Scholar]
  80. 80.
    Nandakumar J, Schwer B, Schaffrath R, Shuman S. 2008. RNA repair: an antidote to cytotoxic eukaryal RNA damage. Mol. Cell 31:278–86
    [Google Scholar]
  81. 81.
    Nandakumar J, Shuman S. 2004. How an RNA ligase discriminates RNA versus DNA damage. Mol. Cell 16:211–21
    [Google Scholar]
  82. 82.
    Novogrodsky A, Hurwitz J. 1966. The enzymatic phosphorylation of ribonucleic acid and deoxyribonucleic acid: phosphorylation at 5′-hydroxyl termini. J. Biol. Chem. 241:2923–32
    [Google Scholar]
  83. 83.
    Novogrodsky A, Tal M, Traub A, Hurwitz J. 1966. The enzymatic phosphorylation of ribonucleic acid and deoxyribonucleic acid: further properties of the 5′-hydroxyl polynucleotide kinase. J. Biol. Chem. 241:2933–43
    [Google Scholar]
  84. 84.
    O'Farrell PZ, Cordell B, Valenzuela P, Rutter WJ, Goodman HM. 1978. Structure and processing of yeast precursor tRNAs containing intervening sequences. Nature 274:438–45
    [Google Scholar]
  85. 85.
    Okada C, Maegawa Y, Yao M, Tanaka I. 2006. Crystal structure of an RtcB homolog protein (PH1502-extein protein) from Pyrococcus horikoshii reveals a novel fold. Proteins 63:1119–22
    [Google Scholar]
  86. 86.
    Penner M, Morad I, Snyder L, Kaufmann G. 1995. Phage T4-coded Stp: double-edged effector of coupled DNA and tRNA-restriction systems. J. Mol. Biol. 249:857–68
    [Google Scholar]
  87. 87.
    Peschek J, Walter P. 2019. tRNA ligase structure reveals kinetic competition between non-conventional mRNA splicing and mRNA decay. eLife 8:e44199
    [Google Scholar]
  88. 88.
    Phizicky EM, Consaul SA, Nehrke KW, Abelson J. 1992. Yeast tRNA ligase mutants are nonviable and accumulate tRNA splicing intermediates. J. Biol. Chem. 267:4577–82
    [Google Scholar]
  89. 89.
    Phizicky EM, Schwartz RC, Abelson J. 1986. Saccharomyces cerevisiae tRNA ligase. Purification of the protein and isolation of the structural gene. J. Biol. Chem. 261:2978–86
    [Google Scholar]
  90. 90.
    Pick L, Furneaux H, Hurwitz J. 1986. Purification of wheat germ RNA ligase. II. Mechanism of action of wheat germ RNA ligase. J. Biol. Chem. 261:6694–704
    [Google Scholar]
  91. 91.
    Pick L, Hurwitz J. 1986. Purification of wheat germ RNA ligase. I. Characterization of a ligase-associated 5′-hydroxyl polynucleotide kinase activity. J. Biol. Chem. 261:6684–93
    [Google Scholar]
  92. 92.
    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]
  93. 93.
    Popow J, Jurkin J, Schleiffer A, Martinez J. 2014. Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors. Nature 511:104–7
    [Google Scholar]
  94. 94.
    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]
  95. 95.
    Remus BS, Goldgur Y, Shuman S. 2017. Structural basis for the GTP specificity of the RNA kinase domain of fungal tRNA ligase. Nucleic Acids Res. 45:12945–53
    [Google Scholar]
  96. 96.
    Remus BS, Schwer B, Shuman S. 2016. Characterization of the tRNA ligases of pathogenic fungi Aspergillus fumigatus and Coccidioides immitis. RNA 22:1500–9
    [Google Scholar]
  97. 97.
    Remus BS, Shuman S. 2013. A kinetic framework for tRNA ligase and enforcement of a 2′-phosphate requirement for ligation highlights the design logic of an RNA repair machine. RNA 19:659–69
    [Google Scholar]
  98. 98.
    Remus BS, Shuman S. 2014. Distinctive kinetics and substrate specificities of plant and fungal tRNA ligases. RNA 20:462–73
    [Google Scholar]
  99. 99.
    Richardson CC. 1965. Phosphorylation of nucleic acid by an enzyme from T4 bacteriophage-infected Escherichia coli. . PNAS 54:158–65
    [Google Scholar]
  100. 100.
    Runnels JM, Soltis D, Hey T, Snyder L. 1982. Genetic and physiological studies of the role of the RNA ligase of bacteriophage T4. J. Mol. Biol. 154:273–86
    [Google Scholar]
  101. 101.
    Sawaya R, Schwer B, Shuman S. 2003. Genetic and biochemical analysis of the functional domains of yeast tRNA ligase. J. Biol. Chem. 278:43298–398
    [Google Scholar]
  102. 102.
    Sawaya R, Schwer B, Shuman S. 2005. Structure–function analysis of the yeast NAD+-dependent tRNA 2′-phosphotransferase Tpt1. RNA 11:107–13
    [Google Scholar]
  103. 103.
    Schwer B, Aronova A, Ramirez A, Braun P, Shuman S. 2008. Mammalian 2′,3′ cyclic nucleotide phosphodiesterase (CNP) can function as a tRNA splicing enzyme in vivo. RNA 14:204–10
    [Google Scholar]
  104. 104.
    Schwer B, Sawaya R, Ho CK, Shuman S. 2004. Portability and fidelity of RNA-repair systems. PNAS 101:2788–93
    [Google Scholar]
  105. 105.
    Sekulovski S, Devant P, Panizza S, Gogakos T, Pitiriciu A et al. 2021. Assembly defects of human tRNA splicing endonuclease contribute to impaired pre-tRNA processing in pontocerebellar hypoplasia. Nat. Commun. 12:5610
    [Google Scholar]
  106. 106.
    Shuman S, Lima CD. 2004. The polynucleotide ligase and RNA capping enzyme superfamily of covalent nucleotidyltransferases. Curr. Opin. Struct. Biol. 14:757–64
    [Google Scholar]
  107. 107.
    Sidrauski C, Cox JS, Walter P. 1996. tRNA ligase is required for regulated mRNA splicing in the unfolded protein response. Cell 87:405–13
    [Google Scholar]
  108. 108.
    Silber R, Malathi VG, Hurwitz J. 1972. Purification and properties of bacteriophage T4-induced RNA ligase. PNAS 69:3009–13
    [Google Scholar]
  109. 109.
    Smith P, Wang LK, Nair PA, Shuman S. 2012. The adenylyltransferase domain of bacterial Pnkp defines a unique RNA ligase family. PNAS 109:2296–301
    [Google Scholar]
  110. 110.
    Spinelli SL, Consaul SA, Phizicky EM. 1997. A conditional lethal yeast phosphotransferase mutant accumulates tRNA with a 2′-phosphate and an unmodified base at the splice junction. RNA 3:1388–400
    [Google Scholar]
  111. 111.
    Spinelli SL, Kierzek R, Turner DH, Phizicky EM. 1999. Transient ADP-ribosylation of a 2′-phosphate implicated in its removal from ligated tRNA during splicing in yeast. J. Biol. Chem. 274:2637–44
    [Google Scholar]
  112. 112.
    Spinelli SL, Malik HS, Consaul SA, Phizicky EM. 1998. A functional homolog of a yeast tRNA splicing enzyme is conserved in higher eukaryotes and in Escherichia coli. PNAS 95:14136–41
    [Google Scholar]
  113. 113.
    Steiger MA, Jackman JE, Phizicky EM. 2005. Analysis of 2′-phosphotransferase (Tpt1p) from Saccharomyces cerevisiae: evidence for a conserved two-step reaction mechanism. RNA 11:99–106
    [Google Scholar]
  114. 114.
    Tanaka N, Chakravarty AK, Maughan B, Shuman S. 2011. Novel mechanism of RNA repair by RtcB via sequential 2′,3′-cyclic phosphodiesterase and 3′-phosphate/5′-hydroxyl ligation reactions. J. Biol. Chem. 286:43134–43
    [Google Scholar]
  115. 115.
    Tanaka N, Meineke B, Shuman S. 2011. RtcB, a novel RNA ligase, can catalyze tRNA splicing and HAC1 mRNA splicing in vivo. J. Biol. Chem. 286:30253–57
    [Google Scholar]
  116. 116.
    Tanaka N, Shuman S. 2011. RtcB is the RNA ligase component of an Escherichia coli RNA repair operon. J. Biol. Chem. 286:7727–31
    [Google Scholar]
  117. 117.
    Tao P, Wu X, Tang WC, Zhu J, Rao V. 2017. Engineering of bacteriophage T4 genome using CRISPR-Cas9. ACS Synth. Biol. 6:1952–61
    [Google Scholar]
  118. 118.
    Temmel H, Müller C, Sauert M, Vesper O, Reiss A et al. 2017. The RNA ligase RtcB reverses MazF-induced ribosome heterogeneity in Escherichia coli. Nucleic Acids Res. 45:4708–21
    [Google Scholar]
  119. 119.
    Thogersen HC, Morris HR, Rand KN, Gait MJ. 1985. Location of the adenylylation site in T4 RNA ligase. Eur. J. Biochem. 147:325–29
    [Google Scholar]
  120. 120.
    Tian Y, Zeng F, Raybarman A, Fatma S, Carruthers A et al. 2022. Sequential rescue and repair of stalled and damaged ribosome by bacterial PrfH and RtcB. PNAS 119:e2202464119
    [Google Scholar]
  121. 121.
    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]
  122. 122.
    Unciuleac MC, Goldgur Y, Shuman S. 2017. Two-metal versus one-metal mechanisms of lysine adenylylation by ATP-dependent and NAD+-dependent polynucleotide ligases. PNAS 114:2592–97
    [Google Scholar]
  123. 123.
    Unlu I, Lu Y, Wang X. 2018. The cyclic phosphodiesterase CNP and RNA cyclase RtcA fine-tune noncanonical XBP1 splicing during ER stress. J. Biol. Chem. 293:19365–76
    [Google Scholar]
  124. 124.
    Valenzuela P, Venegas A, Weinberg F, Bishop R, Rutter WJ. 1978. Structure of yeast phenylalanine-tRNA genes: an intervening DNA segment within the region coding for the tRNA. PNAS 75:190–94
    [Google Scholar]
  125. 125.
    Wang LK, Lima CD, Shuman S. 2002. Structure and mechanism of T4 polynucleotide kinase: an RNA repair enzyme. EMBO J. 21:3873–80
    [Google Scholar]
  126. 126.
    Wang LK, Nandakumar J, Schwer B, Shuman S. 2007. The C-terminal domain of T4 RNA ligase 1 confers specificity for tRNA repair. RNA 13:1235–44
    [Google Scholar]
  127. 127.
    Wang LK, Schwer B, Englert M, Beier H, Shuman S. 2006. Structure–function analysis of the kinase-CPD domain of yeast tRNA ligase (Trl1) and requirements for complementation of tRNA splicing by a plant Trl1 homolog. Nucleic Acids Res. 34:517–27
    [Google Scholar]
  128. 128.
    Wang LK, Shuman S. 2001. Domain structure and mutational analysis of T4 polynucleotide kinase. J. Biol. Chem. 276:26868–74
    [Google Scholar]
  129. 129.
    Wang LK, Shuman S. 2002. Mutational analysis defines the 5′-kinase and 3′-phosphatase active sites of T4 polynucleotide kinase. Nucleic Acids Res. 30:1073–80
    [Google Scholar]
  130. 130.
    Wang LK, Shuman S. 2005. Structure–function analysis of yeast tRNA ligase. RNA 11:966–75
    [Google Scholar]
  131. 131.
    Wang LK, Shuman S. 2010. Mutational analysis of the 5′-OH oligonucleotide phosphate acceptor site of T4 polynucleotide kinase. Nucleic Acids Res. 38:1304–11
    [Google Scholar]
  132. 132.
    Wang LK, Smith P, Shuman S. 2013. Structure and mechanism of the 2′,3′ phosphatase component of the bacterial Pnkp-Hen1 RNA repair system. Nucleic Acids Res. 41:5864–73
    [Google Scholar]
  133. 133.
    Wang P, Chan CM, Christensen D, Zhang C, Selvadurai K, Huang RH. 2012. Molecular basis of bacterial protein Hen1 activating the ligase activity of bacterial protein Pnkp for RNA repair. PNAS 109:13248–53
    [Google Scholar]
  134. 134.
    Wang P, Selvadurai K, Huang RH. 2015. Reconstitution and structure of a bacterial Pnkp1-Rnl-Hen1 RNA repair complex. Nat. Commun. 6:6876
    [Google Scholar]
  135. 135.
    Westaway SK, Phizicky EM, Abelson J. 1988. Structure and function of the yeast tRNA ligase gene. J. Biol. Chem. 263:3171–76
    [Google Scholar]
  136. 136.
    Wu J, Hopper AK. 2014. Healing for destruction: tRNA intron degradation in yeast is a two-step cytoplasmic process catalyzed by tRNA ligase Rlg1 and 5′-to-3′ exonuclease Xrn1. Genes Dev. 28:1556–61
    [Google Scholar]
  137. 137.
    Yuan Y, Stumpf FM, Schlor LA, Schmidt OP, Saumer P et al. 2023. Chemoproteomic discovery of a human RNA ligase. Nat. Comm. 14:842
    [Google Scholar]
  138. 138.
    Zhang C, Chan CM, Wang P, Huang RH. 2012. Probing the substrate specificity of the bacterial Pnkp/Hen1 RNA repair system using synthetic RNAs. RNA 18:335–44
    [Google Scholar]
  139. 139.
    Zhu H, Smith P, Wang LK, Shuman S. 2007. Structure-function analysis of the 3′-phosphatase component of T4 polynucleotide kinase/phosphatase. Virology 366:126–36
    [Google Scholar]
  140. 140.
    Zillmann M, Gorovsky MA, Phizicky EM. 1991. Conserved mechanism of tRNA splicing in eukaryotes. Mol. Cell. Biol. 11:5410–16
    [Google Scholar]
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