Skip to main content
SpringerLink
Log in

Non-catalytic Regulation of Gene Expression by Aminoacyl-tRNA Synthetases

  • Chapter
  • First Online:
Aminoacyl-tRNA Synthetases in Biology and Medicine

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 344))

Abstract

Aminoacyl-tRNA synthetases (AARSs) are a group of essential and ubiquitous “house-keeping” enzymes responsible for charging corresponding amino acids to their cognate transfer RNAs (tRNAs) and providing the correct substrates for high-fidelity protein synthesis. During the last three decades, wide-ranging biochemical and genetic studies have revealed non-catalytic regulatory functions of multiple AARSs in biological processes including gene transcription, mRNA translation, and mitochondrial RNA splicing, and in diverse species from bacteria through yeasts to vertebrates. Remarkably, ongoing exploration of non-canonical functions of AARSs has shown that they contribute importantly to control of inflammation, angiogenesis, immune response, and tumorigenesis, among other critical physiopathological processes. In this chapter we consider the non-canonical functions of AARSs in regulating gene expression by mechanisms not directly related to their enzymatic activities, namely, at the levels of mRNA production, processing, and translation. The scope of AARS-mediated gene regulation ranges from negative autoregulation of single AARS genes to gene-selective control, and ultimately to global gene regulation. Clearly, AARSs have evolved these auxiliary regulatory functions that optimize the survival and well-being of the organism, possibly with more complex regulatory mechanisms associated with more complex organisms. In the first section on transcriptional control, we introduce the roles of autoregulation by Escherichia coli AlaRS, transcriptional activation by human LysRS, and transcriptional inhibition by vertebrate SerRS. In the second section on translational control, we recapitulate the roles of GluProRS in translation repression at the initiation step, auto-inhibition of E. coli thrS mRNA translation by ThrRS, and global translational arrest by phosphorylated human MetRS. Finally, in the third section, we describe the RNA splicing activities of mitochondrial TyrRS and LeuRS in Neurospora and yeasts, respectively.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 299.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ibba M, Soll D (2000) Aminoacyl-tRNA synthesis. Annu Rev Biochem 69:617–650

    CAS  Google Scholar 

  2. Ribas de Pouplana L, Schimmel P (2001) Aminoacyl-tRNA synthetases: potential markers of genetic code development. Trends Biochem Sci 26:591–596

    CAS  Google Scholar 

  3. Yuan J, O’Donoghue P, Ambrogelly A, Gundllapalli S, Sherrer RL, Palioura S, Simonovic M, Soll D (2010) Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl-tRNA formation systems. FEBS Lett 584:342–349

    CAS  Google Scholar 

  4. Brandao MM, Silva-Filho MC (2011) Evolutionary history of Arabidopsis thaliana aminoacyl-tRNA synthetase dual-targeted proteins. Mol Biol Evol 28:79–85

    CAS  Google Scholar 

  5. Jackson KE, Habib S, Frugier M, Hoen R, Khan S, Pham JS, Ribas de Pouplana L, Royo M, Santos MA, Sharma A, Ralph SA (2011) Protein translation in Plasmodium parasites. Trends Parasitol 27:467–476

    CAS  Google Scholar 

  6. Eriani G, Delarue M, Poch O, Gangloff J, Moras D (1990) Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature 347:203–206

    CAS  Google Scholar 

  7. Cusack S, Berthet-Colominas C, Hartlein M, Nassar N, Leberman R (1990) A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A. Nature 347:249–255

    CAS  Google Scholar 

  8. Ling J, Reynolds N, Ibba M (2009) Aminoacyl-tRNA synthesis and translational quality control. Annu Rev Microbiol 63:61–78

    CAS  Google Scholar 

  9. Martinis SA, Boniecki MT (2010) The balance between pre- and post-transfer editing in tRNA synthetases. FEBS Lett 584:455–459

    CAS  Google Scholar 

  10. Martinis SA, Plateau P, Cavarelli J, Florentz C (1999) Aminoacyl-tRNA synthetases: a family of expanding functions. Mittelwihr, France, October 10–15, 1999. EMBO J 18:4591–4596

    CAS  Google Scholar 

  11. Park SG, Schimmel P, Kim S (2008) Aminoacyl tRNA synthetases and their connections to disease. Proc Natl Acad Sci U S A 105:11043–11049

    CAS  Google Scholar 

  12. Kim S, You S, Hwang D (2011) Aminoacyl-tRNA synthetases and tumorigenesis: more than housekeeping. Nat Rev Cancer 11:708–718

    CAS  Google Scholar 

  13. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5:101–113

    CAS  Google Scholar 

  14. Shiba K (2002) Intron positions delineate the evolutionary path of a pervasively appended peptide in five human aminoacyl-tRNA synthetases. J Mol Evol 55:727–733

    CAS  Google Scholar 

  15. Ray PS, Sullivan JC, Jia J, Francis J, Finnerty JR, Fox PL (2011) Evolution of function of a fused metazoan tRNA synthetase. Mol Biol Evol 28:437–447

    CAS  Google Scholar 

  16. Guo M, Yang XL, Schimmel P (2010) New functions of aminoacyl-tRNA synthetases beyond translation. Nat Rev Mol Cell Biol 11:668–674

    CAS  Google Scholar 

  17. Rho SB, Kim MJ, Lee JS, Seol W, Motegi H, Kim S, Shiba K (1999) Genetic dissection of protein-protein interactions in multi-tRNA synthetase complex. Proc Natl Acad Sci U S A 96:4488–4493

    CAS  Google Scholar 

  18. Robinson JC, Kerjan P, Mirande M (2000) Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly. J Mol Biol 304:983–994

    CAS  Google Scholar 

  19. Kyriacou SV, Deutscher MP (2008) An important role for the multienzyme aminoacyl-tRNA synthetase complex in mammalian translation and cell growth. Mol Cell 29:419–427

    CAS  Google Scholar 

  20. Nathanson L, Deutscher MP (2000) Active aminoacyl-tRNA synthetases are present in nuclei as a high molecular weight multienzyme complex. J Biol Chem 275:31559–31562

    CAS  Google Scholar 

  21. Sajish M, Zhou Q, Kishi S, Valdez DM Jr, Kapoor M, Guo M, Lee S, Kim S, Yang XL, Schimmel P (2012) Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-gamma and p53 signaling. Nat Chem Biol 8:547–554

    CAS  Google Scholar 

  22. Fu G, Xu T, Shi Y, Wei N, Yang XL (2012) tRNA-controlled nuclear import of a human tRNA synthetase. J Biol Chem 287:9330–9334

    CAS  Google Scholar 

  23. Putzer H, Grunberg-Manago M, Springer M (1995) Bacterial aminoacyl-tRNA synthetases: genes and regulation of expression. In: Söll D, RajBhandary UL (eds) tRNA: structure, biosynthesis, and function. American Society for Microbiology, Washington, DC, pp 293–333

    Google Scholar 

  24. Grundy FJ, Henkin TM (1993) tRNA as a positive regulator of transcription antitermination in B. subtilis. Cell 74:475–482

    CAS  Google Scholar 

  25. Putney SD, Royal NJ, Neuman de Vegvar H, Herlihy WC, Biemann K, Schimmel P (1981) Primary structure of a large aminoacyl-tRNA synthetase. Science 213:1497–1501

    CAS  Google Scholar 

  26. Putney SD, Schimmel P (1981) An aminoacyl tRNA synthetase binds to a specific DNA sequence and regulates its gene transcription. Nature 291:632–635

    CAS  Google Scholar 

  27. Lechler A, Kreutzer R (1998) The phenylalanyl-tRNA synthetase specifically binds DNA. J Mol Biol 278:897–901

    CAS  Google Scholar 

  28. Dou X, Limmer S, Kreutzer R (2001) DNA-binding of phenylalanyl-tRNA synthetase is accompanied by loop formation of the double-stranded DNA. J Mol Biol 305:451–458

    CAS  Google Scholar 

  29. Finarov I, Moor N, Kessler N, Klipcan L, Safro MG (2010) Structure of human cytosolic phenylalanyl-tRNA synthetase: evidence for kingdom-specific design of the active sites and tRNA binding patterns. Structure 18:343–353

    CAS  Google Scholar 

  30. Hilderman RH, Ortwerth BJ (1987) A preferential role for lysyl-tRNA4 in the synthesis of diadenosine 5′,5″′-P1, P4-tetraphosphate by an arginyl-tRNA synthetase-lysyl-tRNA synthetase complex from rat liver. Biochemistry 26:1586–1591

    CAS  Google Scholar 

  31. Brevet A, Plateau P, Cirakoglu B, Pailliez JP, Blanquet S (1982) Zinc-dependent synthesis of 5′,5′-diadenosine tetraphosphate by sheep liver lysyl- and phenylalanyl-tRNA synthetases. J Biol Chem 257:14613–14615

    CAS  Google Scholar 

  32. Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (2009) LysRS serves as a key signaling molecule in the immune response by regulating gene expression. Mol Cell 34:603–611

    CAS  Google Scholar 

  33. Lee YN, Nechushtan H, Figov N, Razin E (2004) The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcεRI-activated mast cells. Immunity 20:145–151

    CAS  Google Scholar 

  34. Tammela T, Enholm B, Alitalo K, Paavonen K (2005) The biology of vascular endothelial growth factors. Cardiovasc Res 65:550–563

    CAS  Google Scholar 

  35. Coultas L, Chawengsaksophak K, Rossant J (2005) Endothelial cells and VEGF in vascular development. Nature 438:937–945

    CAS  Google Scholar 

  36. Fukui H, Hanaoka R, Kawahara A (2009) Noncanonical activity of seryl-tRNA synthetase is involved in vascular development. Circ Res 104:1253–1259

    CAS  Google Scholar 

  37. Herzog W, Muller K, Huisken J, Stainier DY (2009) Genetic evidence for a noncanonical function of seryl-tRNA synthetase in vascular development. Circ Res 104:1260–1266

    CAS  Google Scholar 

  38. Jin SW, Herzog W, Santoro MM, Mitchell TS, Frantsve J, Jungblut B, Beis D, Scott IC, D’Amico LA, Ober EA, Verkade H, Field HA, Chi NC, Wehman AM, Baier H, Stainier DY (2007) A transgene-assisted genetic screen identifies essential regulators of vascular development in vertebrate embryos. Dev Biol 307:29–42

    CAS  Google Scholar 

  39. Xu X, Shi Y, Zhang HM, Swindell EC, Marshall AG, Guo M, Kishi S, Yang XL (2012) Unique domain appended to vertebrate tRNA synthetase is essential for vascular development. Nat Commun 3:681

    Google Scholar 

  40. Springer M, Plumbridge JA, Butler JS, Graffe M, Dondon J, Mayaux JF, Fayat G, Lestienne P, Blanquet S, Grunberg-Manago M (1985) Autogenous control of Escherichia coli threonyl-tRNA synthetase expression in vivo. J Mol Biol 185:93–104

    CAS  Google Scholar 

  41. Moine H, Romby P, Springer M, Grunberg-Manago M, Ebel JP, Ehresmann B, Ehresmann C (1990) Escherichia coli threonyl-tRNA synthetase and tRNAThr modulate the binding of the ribosome to the translational initiation site of the thrS mRNA. J Mol Biol 216:299–310

    CAS  Google Scholar 

  42. Romby P, Caillet J, Ebel C, Sacerdot C, Graffe M, Eyermann F, Brunel C, Moine H, Ehresmann C, Ehresmann B, Springer M (1996) The expression of E. coli threonyl-tRNA synthetase is regulated at the translational level by symmetrical operator-repressor interactions. EMBO J 15:5976–5987

    CAS  Google Scholar 

  43. Romby P, Brunel C, Caillet J, Springer M, Grunberg-Manago M, Westhof E, Ehresmann C, Ehresmann B (1992) Molecular mimicry in translational control of E. coli threonyl-tRNA synthetase gene. Competitive inhibition in tRNA aminoacylation and operator-repressor recognition switch using tRNA identity rules. Nucleic Acids Res 20:5633–5640

    CAS  Google Scholar 

  44. Sankaranarayanan R, Dock-Bregeon AC, Romby P, Caillet J, Springer M, Rees B, Ehresmann C, Ehresmann B, Moras D (1999) The structure of threonyl-tRNA synthetase-tRNAThr complex enlightens its repressor activity and reveals an essential zinc ion in the active site. Cell 97:371–381

    CAS  Google Scholar 

  45. Torres-Larios A, Dock-Bregeon AC, Romby P, Rees B, Sankaranarayanan R, Caillet J, Springer M, Ehresmann C, Ehresmann B, Moras D (2002) Structural basis of translational control by Escherichia coli threonyl tRNA synthetase. Nat Struct Biol 9:343–347

    CAS  Google Scholar 

  46. Caillet J, Nogueira T, Masquida B, Winter F, Graffe M, Dock-Bregeon AC, Torres-Larios A, Sankaranarayanan R, Westhof E, Ehresmann B, Ehresmann C, Romby P, Springer M (2003) The modular structure of Escherichia coli threonyl-tRNA synthetase as both an enzyme and a regulator of gene expression. Mol Microbiol 47:961–974

    CAS  Google Scholar 

  47. Brunel C, Caillet J, Lesage P, Graffe M, Dondon J, Moine H, Romby P, Ehresmann C, Ehresmann B, Grunberg-Manago M et al (1992) Domains of the Escherichia coli threonyl-tRNA synthetase translational operator and their relation to threonine tRNA isoacceptors. J Mol Biol 227:621–634

    CAS  Google Scholar 

  48. Jenner L, Romby P, Rees B, Schulze-Briese C, Springer M, Ehresmann C, Ehresmann B, Moras D, Yusupova G, Yusupov M (2005) Translational operator of mRNA on the ribosome: how repressor proteins exclude ribosome binding. Science 308:120–123

    CAS  Google Scholar 

  49. Springer M, Graffe M, Butler JS, Grunberg-Manago M (1986) Genetic definition of the translational operator of the threonine-tRNA ligase gene in Escherichia coli. Proc Natl Acad Sci U S A 83:4384–4388

    CAS  Google Scholar 

  50. Mazumder B, Seshadri V, Fox PL (2003) Translational control by the 3′-UTR: the ends specify the means. Trends Biochem Sci 28:91–98

    CAS  Google Scholar 

  51. Cerini C, Kerjan P, Astier M, Gratecos D, Mirande M, Semeriva M (1991) A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase. EMBO J 10:4267–4277

    CAS  Google Scholar 

  52. Kaiser E, Hu B, Becher S, Eberhard D, Schray B, Baack M, Hameister H, Knippers R (1994) The human EPRS locus (formerly the QARS locus): a gene encoding a class I and a class II aminoacyl-tRNA synthetase. Genomics 19:280–290

    CAS  Google Scholar 

  53. Han JM, Kim JY, Kim S (2003) Molecular network and functional implications of macromolecular tRNA synthetase complex. Biochem Biophys Res Commun 303:985–993

    CAS  Google Scholar 

  54. Cahuzac B, Berthonneau E, Birlirakis N, Guittet E, Mirande M (2000) A recurrent RNA-binding domain is appended to eukaryotic aminoacyl-tRNA synthetases. EMBO J 19:445–452

    CAS  Google Scholar 

  55. Jeong EJ, Hwang GS, Kim KH, Kim MJ, Kim S, Kim KS (2000) Structural analysis of multifunctional peptide motifs in human bifunctional tRNA synthetase: identification of RNA-binding residues and functional implications for tandem repeats. Biochemistry 39:15775–15782

    CAS  Google Scholar 

  56. Sampath P, Mazumder B, Seshadri V, Gerber CA, Chavatte L, Kinter M, Ting SM, Dignam JD, Kim S, Driscoll DM, Fox PL (2004) Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation. Cell 119:195–208

    CAS  Google Scholar 

  57. Musci G, Polticelli F, Calabrese L (1999) Structure/function relationships in ceruloplasmin. Adv Exp Med Biol 448:175–182

    CAS  Google Scholar 

  58. Ehrenwald E, Chisolm GM, Fox PL (1994) Intact human ceruloplasmin oxidatively modifies low density lipoprotein. J Clin Invest 93:1493–1501

    CAS  Google Scholar 

  59. Mazumder B, Mukhopadhyay CK, Prok A, Cathcart MK, Fox PL (1997) Induction of ceruloplasmin synthesis by IFN-γ in human monocytic cells. J Immunol 159:1938–1944

    CAS  Google Scholar 

  60. Mazumder B, Fox PL (1999) Delayed translational silencing of ceruloplasmin transcript in gamma interferon-activated U937 monocytic cells: role of the 3′ untranslated region. Mol Cell Biol 19:6898–6905

    CAS  Google Scholar 

  61. Sampath P, Mazumder B, Seshadri V, Fox PL (2003) Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3′ untranslated region. Mol Cell Biol 23:1509–1519

    CAS  Google Scholar 

  62. Mazumder B, Sampath P, Seshadri V, Maitra RK, DiCorleto PE, Fox PL (2003) Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell 115:187–198

    CAS  Google Scholar 

  63. Jia J, Arif A, Ray PS, Fox PL (2008) WHEP domains direct noncanonical function of glutamyl-prolyl tRNA synthetase in translational control of gene expression. Mol Cell 29:679–690

    CAS  Google Scholar 

  64. Arif A, Jia J, Mukhopadhyay R, Willard B, Kinter M, Fox PL (2009) Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity. Mol Cell 35:164–180

    CAS  Google Scholar 

  65. Arif A, Jia J, Moodt RA, DiCorleto PE, Fox PL (2011) Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control. Proc Natl Acad Sci U S A 108:1415–1420

    CAS  Google Scholar 

  66. Ray PS, Arif A, Fox PL (2007) Macromolecular complexes as depots for releasable regulatory proteins. Trends Biochem Sci 32:158–164

    CAS  Google Scholar 

  67. Ray PS, Fox PL (2007) A post-transcriptional pathway represses monocyte VEGF-A expression and angiogenic activity. EMBO J 26:3360–3372

    CAS  Google Scholar 

  68. Mukhopadhyay R, Ray PS, Arif A, Brady AK, Kinter M, Fox PL (2008) DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Mol Cell 32:371–382

    CAS  Google Scholar 

  69. Vyas K, Chaudhuri S, Leaman DW, Komar AA, Musiyenko A, Barik S, Mazumder B (2009) Genome-wide polysome profiling reveals an inflammation-responsive posttranscriptional operon in gamma interferon-activated monocytes. Mol Cell Biol 29:458–470

    CAS  Google Scholar 

  70. Keene JD, Tenenbaum SA (2002) Eukaryotic mRNPs may represent posttranscriptional operons. Mol Cell 9:1161–1167

    CAS  Google Scholar 

  71. Ray PS, Jia J, Yao P, Majumder M, Hatzoglou M, Fox PL (2009) A stress-responsive RNA switch regulates VEGFA expression. Nature 457:915–919

    CAS  Google Scholar 

  72. Arif A, Chatterjee P, Moodt RA, Fox PL (2012) Heterotrimeric GAIT complex drives transcript-selective translation inhibition in murine macrophages. Mol Cell Biol 32:5046–5055

    CAS  Google Scholar 

  73. Stocker R, Keaney JF Jr (2004) Role of oxidative modifications in atherosclerosis. Physiol Rev 84:1381–1478

    CAS  Google Scholar 

  74. Jia J, Arif A, Willard B, Smith JD, Stuehr DJ, Hazen SL, Fox PL (2012) Protection of extraribosomal RPL13a by GAPDH and dysregulation by S-nitrosylation. Mol Cell 47:656–663

    CAS  Google Scholar 

  75. Yao P, Potdar AA, Arif A, Ray PS, Mukhopadhyay R, Willard B, Xu Y, Yan J, Saidel GM, Fox PL (2012) Coding region polyadenylation generates a truncated tRNA synthetase that counters translation repression. Cell 149:88–100

    CAS  Google Scholar 

  76. Yao P, Fox PL (2012) A truncated tRNA synthetase directs a "translational trickle" of gene expression. Cell Cycle 11:1868–1869

    CAS  Google Scholar 

  77. Kwon NH, Kang T, Lee JY, Kim HH, Kim HR, Hong J, Oh YS, Han JM, Ku MJ, Lee SY, Kim S (2011) Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3. Proc Natl Acad Sci U S A 108:19635–19640

    CAS  Google Scholar 

  78. Cech TR (1990) Self-splicing of group I introns. Annu Rev Biochem 59:543–568

    CAS  Google Scholar 

  79. Lambowitz AM, Perlman PS (1990) Involvement of aminoacyl-tRNA synthetases and other proteins in group I and group II intron splicing. Trends Biochem Sci 15:440–444

    Google Scholar 

  80. Labouesse M (1990) The yeast mitochondrial leucyl-tRNA synthetase is a splicing factor for the excision of several group I introns. Mol Gen Genet 224:209–221

    CAS  Google Scholar 

  81. Akins RA, Lambowitz AM (1987) A protein required for splicing group I introns in Neurospora mitochondria is mitochondrial tyrosyl-tRNA synthetase or a derivative thereof. Cell 50:331–345

    CAS  Google Scholar 

  82. Myers CA, Wallweber GJ, Rennard R, Kemel Y, Caprara MG, Mohr G, Lambowitz AM (1996) A tyrosyl-tRNA synthetase suppresses structural defects in the two major helical domains of the group I intron catalytic core. J Mol Biol 262:87–104

    CAS  Google Scholar 

  83. Kamper U, Kuck U, Cherniack AD, Lambowitz AM (1992) The mitochondrial tyrosyl-tRNA synthetase of Podospora anserina is a bifunctional enzyme active in protein synthesis and RNA splicing. Mol Cell Biol 12:499–511

    CAS  Google Scholar 

  84. Mannella CA, Collins RA, Green MR, Lambowitz AM (1979) Defective splicing of mitochondrial rRNA in cytochrome-deficient nuclear mutants of Neurospora crassa. Proc Natl Acad Sci U S A 76:2635–2639

    CAS  Google Scholar 

  85. Collins RA, Lambowitz AM (1985) RNA splicing in Neurospora mitochondria. Defective splicing of mitochondrial mRNA precursors in the nuclear mutant cyt18-1. J Mol Biol 184:413–428

    CAS  Google Scholar 

  86. Mohr G, Zhang A, Gianelos JA, Belfort M, Lambowitz AM (1992) The neurospora CYT-18 protein suppresses defects in the phage T4 td intron by stabilizing the catalytically active structure of the intron core. Cell 69:483–494

    CAS  Google Scholar 

  87. Mohr G, Caprara MG, Guo Q, Lambowitz AM (1994) A tyrosyl-tRNA synthetase can function similarly to an RNA structure in the Tetrahymena ribozyme. Nature 370:147–150

    CAS  Google Scholar 

  88. Paukstelis PJ, Coon R, Madabusi L, Nowakowski J, Monzingo A, Robertus J, Lambowitz AM (2005) A tyrosyl-tRNA synthetase adapted to function in group I intron splicing by acquiring a new RNA binding surface. Mol Cell 17:417–428

    CAS  Google Scholar 

  89. Caprara MG, Lehnert V, Lambowitz AM, Westhof E (1996) A tyrosyl-tRNA synthetase recognizes a conserved tRNA-like structural motif in the group I intron catalytic core. Cell 87:1135–1145

    CAS  Google Scholar 

  90. Caprara MG, Mohr G, Lambowitz AM (1996) A tyrosyl-tRNA synthetase protein induces tertiary folding of the group I intron catalytic core. J Mol Biol 257:512–531

    CAS  Google Scholar 

  91. Webb AE, Rose MA, Westhof E, Weeks KM (2001) Protein-dependent transition states for ribonucleoprotein assembly. J Mol Biol 309:1087–1100

    CAS  Google Scholar 

  92. Myers CA, Kuhla B, Cusack S, Lambowitz AM (2002) tRNA-like recognition of group I introns by a tyrosyl-tRNA synthetase. Proc Natl Acad Sci U S A 99:2630–2635

    CAS  Google Scholar 

  93. Cherniack AD, Garriga G, Kittle JD Jr, Akins RA, Lambowitz AM (1990) Function of Neurospora mitochondrial tyrosyl-tRNA synthetase in RNA splicing requires an idiosyncratic domain not found in other synthetases. Cell 62:745–755

    CAS  Google Scholar 

  94. Kittle JD Jr, Mohr G, Gianelos JA, Wang H, Lambowitz AM (1991) The Neurospora mitochondrial tyrosyl-tRNA synthetase is sufficient for group I intron splicing in vitro and uses the carboxy-terminal tRNA-binding domain along with other regions. Genes Dev 5:1009–1021

    CAS  Google Scholar 

  95. Chen X, Mohr G, Lambowitz AM (2004) The Neurospora crassa CYT-18 protein C-terminal RNA-binding domain helps stabilize interdomain tertiary interactions in group I introns. RNA 10:634–644

    CAS  Google Scholar 

  96. Mohr G, Rennard R, Cherniack AD, Stryker J, Lambowitz AM (2001) Function of the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase in RNA splicing. Role of the idiosyncratic N-terminal extension and different modes of interaction with different group I introns. J Mol Biol 307:75–92

    CAS  Google Scholar 

  97. Guo Q, Lambowitz AM (1992) A tyrosyl-tRNA synthetase binds specifically to the group I intron catalytic core. Genes Dev 6:1357–1372

    CAS  Google Scholar 

  98. Saldanha RJ, Patel SS, Surendran R, Lee JC, Lambowitz AM (1995) Involvement of Neurospora mitochondrial tyrosyl-tRNA synthetase in RNA splicing. A new method for purifying the protein and characterization of physical and enzymatic properties pertinent to splicing. Biochemistry 34:1275–1287

    CAS  Google Scholar 

  99. Saldanha R, Ellington A, Lambowitz AM (1996) Analysis of the CYT-18 protein binding site at the junction of stacked helices in a group I intron RNA by quantitative binding assays and in vitro selection. J Mol Biol 261:23–42

    CAS  Google Scholar 

  100. De La Salle H, Jacq C, Slonimski PP (1982) Critical sequences within mitochondrial introns: pleiotropic mRNA maturase and cis-dominant signals of the box intron controlling reductase and oxidase. Cell 28:721–732

    Google Scholar 

  101. Labouesse M, Netter P, Schroeder R (1984) Molecular basis of the ‘box effect’, a maturase deficiency leading to the absence of splicing of two introns located in two split genes of yeast mitochondrial DNA. Eur J Biochem 144:85–93

    CAS  Google Scholar 

  102. Li GY, Becam AM, Slonimski PP, Herbert CJ (1996) In vitro mutagenesis of the mitochondrial leucyl tRNA synthetase of Saccharomyces cerevisiae shows that the suppressor activity of the mutant proteins is related to the splicing function of the wild-type protein. Mol Gen Genet 252:667–675

    CAS  Google Scholar 

  103. Boniecki MT, Rho SB, Tukalo M, Hsu JL, Romero EP, Martinis SA (2009) Leucyl-tRNA synthetase-dependent and -independent activation of a group I intron. J Biol Chem 284:26243–26250

    CAS  Google Scholar 

  104. Rho SB, Martinis SA (2000) The bI4 group I intron binds directly to both its protein splicing partners, a tRNA synthetase and maturase, to facilitate RNA splicing activity. RNA 6:1882–1894

    CAS  Google Scholar 

  105. Houman F, Rho SB, Zhang J, Shen X, Wang CC, Schimmel P, Martinis SA (2000) A prokaryote and human tRNA synthetase provide an essential RNA splicing function in yeast mitochondria. Proc Natl Acad Sci U S A 97:13743–13748

    CAS  Google Scholar 

  106. Sarkar J, Poruri K, Boniecki MT, McTavish KK, Martinis SA (2012) Yeast mitochondrial leucyl-tRNA synthetase CP1 domain has functionally diverged to accommodate RNA splicing at expense of hydrolytic editing. J Biol Chem 287:14772–14781

    CAS  Google Scholar 

  107. Rho SB, Lincecum TL Jr, Martinis SA (2002) An inserted region of leucyl-tRNA synthetase plays a critical role in group I intron splicing. EMBO J 21:6874–6881

    CAS  Google Scholar 

  108. Cusack S, Yaremchuk A, Tukalo M (2000) The 2 A crystal structure of leucyl-tRNA synthetase and its complex with a leucyl-adenylate analogue. EMBO J 19:2351–2361

    CAS  Google Scholar 

  109. Tukalo M, Yaremchuk A, Fukunaga R, Yokoyama S, Cusack S (2005) The crystal structure of leucyl-tRNA synthetase complexed with tRNALeu in the post-transfer-editing conformation. Nat Struct Mol Biol 12:923–930

    CAS  Google Scholar 

  110. Labouesse M, Herbert CJ, Dujardin G, Slonimski PP (1987) Three suppressor mutations which cure a mitochondrial RNA maturase deficiency occur at the same codon in the open reading frame of the nuclear NAM2 gene. EMBO J 6:713–721

    CAS  Google Scholar 

  111. Palencia A, Crepin T, Vu MT, Lincecum TL Jr, Martinis SA, Cusack S (2012) Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase. Nat Struct Mol Biol 19:677–684

    CAS  Google Scholar 

  112. Hsu JL, Rho SB, Vannella KM, Martinis SA (2006) Functional divergence of a unique C-terminal domain of leucyl-tRNA synthetase to accommodate its splicing and aminoacylation roles. J Biol Chem 281:23075–23082

    CAS  Google Scholar 

  113. Kapasi P, Chaudhuri S, Vyas K, Baus D, Komar AA, Fox PL, Merrick WC, Mazumder B (2007) L13a blocks 48S assembly: role of a general initiation factor in mRNA-specific translational control. Mol Cell 25:113–126

    CAS  Google Scholar 

  114. Ofir-Birin Y, Fang P, Bennett SP, Zhang HM, Wang J, Rachmin I, Shapiro R, Song J, Dagan A, Pozo J, Kim S, Marshall AG, Schimmel P, Yang XL, Nechushtan H, Razin E, Guo M (2012) Structural switch of lysyl-tRNA synthetase between translation and transcription. Mol Cell 49:30–42

    Google Scholar 

Download references

Acknowledgements

This work was supported in part by National Institutes of Health grants P01 HL029582, P01 HL076491, R01 GM086430, and R01 DK083359 to P.L.F., and National Science Foundation grant MCB 0843611 to S.A.M. P.Y. was supported by a Postdoctoral Fellowship from the American Heart Association, Great Rivers Affiliate.

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Peng Yao & Paul L. Fox

  2. Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Kiran Poruri & Susan A. Martinis

Authors
  1. Peng Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kiran Poruri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susan A. Martinis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul L. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul L. Fox .

Editor information

Editors and Affiliations

  1. Department of Molecular Medicine and Biopharmaceutical Sciences, Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Korea, Republic of (South Korea)

    Sunghoon Kim

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Yao, P., Poruri, K., Martinis, S.A., Fox, P.L. (2013). Non-catalytic Regulation of Gene Expression by Aminoacyl-tRNA Synthetases. In: Kim, S. (eds) Aminoacyl-tRNA Synthetases in Biology and Medicine. Topics in Current Chemistry, vol 344. Springer, Dordrecht. https://doi.org/10.1007/128_2013_422

Download citation

Publish with us

Policies and ethics

Search

Navigation