Modification of tRNA by Elongator Is Essential for Efficient Translation of Stress mRNAs
The Elongator complex, including the histone acetyl transferase Sin3/Elp3, was isolated as an RNA polymerase II-interacting complex, and cells deficient in Elongator subunits display transcriptional defects. However, it has also been shown that Elongator mediates the modification of some tRNAs, modulating translation efficiency. We show here that the fission yeast Sin3/Elp3 is important for oxidative stress survival. The stress transcriptional program, governed by the Sty1-Atf1-Pcr1 pathway, is affected in mutant cells, but not severely. On the contrary, cells lacking Sin3/Elp3 cannot modify the uridine wobble nucleoside of certain tRNAs, and other tRNA modifying activities such as Ctu1-Ctu2 are also essential for normal tolerance to H2O2. In particular, a plasmid over-expressing the tRNALysUUU complements the stress-related phenotypes of Sin3/Elp3 mutant cells. We have determined that the main H2O2-dependent genes, including those coding for the transcription factors Atf1 and Pcr1, are highly expressed mRNAs containing a biased number of lysine-coding codons AAA versus AAG. Thus, their mRNAs are poorly translated after stress in cells lacking Sin3/Elp3 or Ctu2, whereas a mutated atf1 transcript with AAA-to-AAG lysine codons is efficiently translated in all strain backgrounds. Our study demonstrates that the lack of a functional Elongator complex results in stress phenotypes due to its contribution to tRNA modification and subsequent translation inefficiency of certain stress-induced, highly expressed mRNAs. These results suggest that the transcriptional defects of these strain backgrounds may be a secondary consequence of the deficient expression of a transcription factor, Atf1-Pcr1, and other components of the transcriptional machinery.
Vyšlo v časopise:
Modification of tRNA by Elongator Is Essential for Efficient Translation of Stress mRNAs. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003647
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003647
Souhrn
The Elongator complex, including the histone acetyl transferase Sin3/Elp3, was isolated as an RNA polymerase II-interacting complex, and cells deficient in Elongator subunits display transcriptional defects. However, it has also been shown that Elongator mediates the modification of some tRNAs, modulating translation efficiency. We show here that the fission yeast Sin3/Elp3 is important for oxidative stress survival. The stress transcriptional program, governed by the Sty1-Atf1-Pcr1 pathway, is affected in mutant cells, but not severely. On the contrary, cells lacking Sin3/Elp3 cannot modify the uridine wobble nucleoside of certain tRNAs, and other tRNA modifying activities such as Ctu1-Ctu2 are also essential for normal tolerance to H2O2. In particular, a plasmid over-expressing the tRNALysUUU complements the stress-related phenotypes of Sin3/Elp3 mutant cells. We have determined that the main H2O2-dependent genes, including those coding for the transcription factors Atf1 and Pcr1, are highly expressed mRNAs containing a biased number of lysine-coding codons AAA versus AAG. Thus, their mRNAs are poorly translated after stress in cells lacking Sin3/Elp3 or Ctu2, whereas a mutated atf1 transcript with AAA-to-AAG lysine codons is efficiently translated in all strain backgrounds. Our study demonstrates that the lack of a functional Elongator complex results in stress phenotypes due to its contribution to tRNA modification and subsequent translation inefficiency of certain stress-induced, highly expressed mRNAs. These results suggest that the transcriptional defects of these strain backgrounds may be a secondary consequence of the deficient expression of a transcription factor, Atf1-Pcr1, and other components of the transcriptional machinery.
Zdroje
1. VivancosAP, JaraM, ZuinA, SansoM, HidalgoE (2006) Oxidative stress in Schizosaccharomyces pombe: different H2O2 levels, different response pathways. Mol Genet Genomics 276: 495–502.
2. VealEA, DayAM, MorganBA (2007) Hydrogen peroxide sensing and signaling. Mol Cell 26: 1–14.
3. ChenD, TooneWM, MataJ, LyneR, BurnsG, et al. (2003) Global transcriptional responses of fission yeast to environmental stress. Mol Biol Cell 14: 214–229.
4. ChenD, WilkinsonCR, WattS, PenkettCJ, TooneWM, et al. (2008) Multiple pathways differentially regulate global oxidative stress responses in fission yeast. Mol Biol Cell 19: 308–317.
5. SansoM, Vargas-PerezI, GarciaP, AyteJ, HidalgoE (2011) Nuclear roles and regulation of chromatin structure by the stress-dependent MAP kinase Sty1 of Schizosaccharomyces pombe. Mol Microbiol 82: 542–554.
6. JohnssonA, Xue-FranzenY, LundinM, WrightAP (2006) Stress-specific role of fission yeast Gcn5 histone acetyltransferase in programming a subset of stress response genes. Eukaryot Cell 5: 1337–1346.
7. SansoM, Vargas-PerezI, QuintalesL, AntequeraF, AyteJ, et al. (2011) Gcn5 facilitates Pol II progression, rather than recruitment to nucleosome-depleted stress promoters, in Schizosaccharomyces pombe. Nucleic Acids Res 39: 6369–6379.
8. WittschiebenBO, FellowsJ, DuW, StillmanDJ, SvejstrupJQ (2000) Overlapping roles for the histone acetyltransferase activities of SAGA and elongator in vivo. Embo J 19: 3060–3068.
9. WinklerGS, KristjuhanA, Erdjument-BromageH, TempstP, SvejstrupJQ (2002) Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo. Proc Natl Acad Sci U S A 99: 3517–3522.
10. SvejstrupJQ (2007) Elongator complex: how many roles does it play? Curr Opin Cell Biol 19: 331–336.
11. HeyerWD, ThuriauxP, KohliJ, EbertP, KerstenH, et al. (1984) An antisuppressor mutation of Schizosaccharomyces pombe affects the post-transcriptional modification of the “wobble” base in the anticodon of tRNAs. J Biol Chem 259: 2856–2862.
12. HuangB, JohanssonMJ, BystromAS (2005) An early step in wobble uridine tRNA modification requires the Elongator complex. Rna 11: 424–436.
13. MehlgartenC, JablonowskiD, WrackmeyerU, TschitschmannS, SondermannD, et al. (2010) Elongator function in tRNA wobble uridine modification is conserved between yeast and plants. Mol Microbiol 76: 1082–1094.
14. ChenC, TuckS, BystromAS (2009) Defects in tRNA modification associated with neurological and developmental dysfunctions in Caenorhabditis elegans elongator mutants. PLoS Genet 5: e1000561.
15. EsbergA, HuangB, JohanssonMJ, BystromAS (2006) Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Mol Cell 24: 139–148.
16. ChenC, HuangB, EliassonM, RydenP, BystromAS (2011) Elongator complex influences telomeric gene silencing and DNA damage response by its role in wobble uridine tRNA modification. PLoS Genet 7: e1002258.
17. VerseesW, De GroeveS, Van LijsebettensM (2010) Elongator, a conserved multitasking complex? Mol Microbiol 76: 1065–1069.
18. AgrisPF, VendeixFA, GrahamWD (2007) tRNA's wobble decoding of the genome: 40 years of modification. J Mol Biol 366: 1–13.
19. KrugerMK, PedersenS, HagervallTG, SorensenMA (1998) The modification of the wobble base of tRNAGlu modulates the translation rate of glutamic acid codons in vivo. J Mol Biol 284: 621–631.
20. UrbonaviciusJ, QianQ, DurandJM, HagervallTG, BjorkGR (2001) Improvement of reading frame maintenance is a common function for several tRNA modifications. Embo J 20: 4863–4873.
21. PatilA, ChanCT, DyavaiahM, RooneyJP, DedonPC, et al. (2012) Translational infidelity-induced protein stress results from a deficiency in Trm9-catalyzed tRNA modifications. RNA Biol 9: 990–1001.
22. AgrisPF, SollD, SenoT (1973) Biological function of 2-thiouridine in Escherichia coli glutamic acid transfer ribonucleic acid. Biochemistry 12: 4331–4337.
23. SylversLA, RogersKC, ShimizuM, OhtsukaE, SollD (1993) A 2-thiouridine derivative in tRNAGlu is a positive determinant for aminoacylation by Escherichia coli glutamyl-tRNA synthetase. Biochemistry 32: 3836–3841.
24. CusackS, YaremchukA, TukaloM (1996) The crystal structures of T. thermophilus lysyl-tRNA synthetase complexed with E. coli tRNA(Lys) and a T. thermophilus tRNA(Lys) transcript: anticodon recognition and conformational changes upon binding of a lysyl-adenylate analogue. Embo J 15: 6321–6334.
25. AshrafSS, SochackaE, CainR, GuentherR, MalkiewiczA, et al. (1999) Single atom modification (O–>S) of tRNA confers ribosome binding. Rna 5: 188–194.
26. BjorkGR, HuangB, PerssonOP, BystromAS (2007) A conserved modified wobble nucleoside (mcm5s2U) in lysyl-tRNA is required for viability in yeast. Rna 13: 1245–1255.
27. NakaiY, NakaiM, HayashiH (2008) Thio-modification of yeast cytosolic tRNA requires a ubiquitin-related system that resembles bacterial sulfur transfer systems. J Biol Chem 283: 27469–27476.
28. HuangB, LuJ, BystromAS (2008) A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae. Rna 14: 2183–2194.
29. SchliekerCD, Van der VeenAG, DamonJR, SpoonerE, PloeghHL (2008) A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway. Proc Natl Acad Sci U S A 105: 18255–18260.
30. NomaA, SakaguchiY, SuzukiT (2009) Mechanistic characterization of the sulfur-relay system for eukaryotic 2-thiouridine biogenesis at tRNA wobble positions. Nucleic Acids Res 37: 1335–1352.
31. LeidelS, PedrioliPG, BucherT, BrostR, CostanzoM, et al. (2009) Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA. Nature 458: 228–232.
32. PedrioliPG, LeidelS, HofmannK (2008) Urm1 at the crossroad of modifications. ‘Protein Modifications: Beyond the Usual Suspects’ Review Series. EMBO Rep 9: 1196–1202.
33. DewezM, BauerF, DieuM, RaesM, VandenhauteJ, et al. (2008) The conserved Wobble uridine tRNA thiolase Ctu1-Ctu2 is required to maintain genome integrity. Proc Natl Acad Sci U S A 105: 5459–5464.
34. BauerF, MatsuyamaA, CandiracciJ, DieuM, ScheligaJ, et al. (2012) Translational control of cell division by Elongator. Cell Reports 1: 1–10.
35. FichtnerL, FrohloffF, BurknerK, LarsenM, BreunigKD, et al. (2002) Molecular analysis of KTI12/TOT4, a Saccharomyces cerevisiae gene required for Kluyveromyces lactis zymocin action. Mol Microbiol 43: 783–791.
36. NugentRL, JohnssonA, FlehartyB, GogolM, Xue-FranzenY, et al. (2010) Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation. BMC Genomics 11: 59.
37. IgloiGL (1988) Interaction of tRNAs and of phosphorothioate-substituted nucleic acids with an organomercurial. Probing the chemical environment of thiolated residues by affinity electrophoresis. Biochemistry 27: 3842–3849.
38. DongH, NilssonL, KurlandCG (1996) Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. J Mol Biol 260: 649–663.
39. PercudaniR, PavesiA, OttonelloS (1997) Transfer RNA gene redundancy and translational selection in Saccharomyces cerevisiae. J Mol Biol 268: 322–330.
40. KanayaS, YamadaY, KudoY, IkemuraT (1999) Studies of codon usage and tRNA genes of 18 unicellular organisms and quantification of Bacillus subtilis tRNAs: gene expression level and species-specific diversity of codon usage based on multivariate analysis. Gene 238: 143–155.
41. TullerT, CarmiA, VestsigianK, NavonS, DorfanY, et al. (2010) An evolutionarily conserved mechanism for controlling the efficiency of protein translation. Cell 141: 344–354.
42. HiraokaY, KawamataK, HaraguchiT, ChikashigeY (2009) Codon usage bias is correlated with gene expression levels in the fission yeast Schizosaccharomyces pombe. Genes Cells 14: 499–509.
43. VetrivelU, ArunkumarV, DorairajS (2007) ACUA: a software tool for automated codon usage analysis. Bioinformation 2: 62–63.
44. KanohJ, WatanabeY, OhsugiM, IinoY, YamamotoM (1996) Schizosaccharomyces pombe gad7+ encodes a phosphoprotein with a bZIP domain, which is required for proper G1 arrest and gene expression under nitrogen starvation. Genes Cells 1: 391–408.
45. ShiozakiK, RussellP (1996) Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes Dev 10: 2276–2288.
46. ChanCT, DyavaiahM, DeMottMS, TaghizadehK, DedonPC, et al. (2010) A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress. PLoS Genet 6: e1001247.
47. ChanCT, PangYL, DengW, BabuIR, DyavaiahM, et al. (2012) Reprogramming of tRNA modifications controls the oxidative stress response by codon-biased translation of proteins. Nat Commun 3: 937.
48. GustiloEM, VendeixFA, AgrisPF (2008) tRNA's modifications bring order to gene expression. Curr Opin Microbiol 11: 134–140.
49. GingoldH, PilpelY (2011) Determinants of translation efficiency and accuracy. Mol Syst Biol 7: 481.
50. GrosjeanH, de Crecy-LagardV, MarckC (2010) Deciphering synonymous codons in the three domains of life: co-evolution with specific tRNA modification enzymes. FEBS Lett 584: 252–264.
51. MaundrellK (1993) Thiamine-repressible expression vectors pREP and pRIP for fission yeast. Gene 123: 127–130.
52. BrunC, DubeyDD, HubermanJA (1995) pDblet, a stable autonomously replicating shuttle vector for Schizosaccharomyces pombe. Gene 164: 173–177.
53. VivancosAP, CastilloEA, BiteauB, NicotC, AyteJ, et al. (2005) A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the antioxidant Pap1 pathway. Proc Natl Acad Sci U S A 102: 8875–8880.
54. SansoM, GogolM, AyteJ, SeidelC, HidalgoE (2008) Transcription factors Pcr1 and Atf1 have distinct roles in stress- and Sty1-dependent gene regulation. Eukaryot Cell 7: 826–835.
55. MorenoS, KlarA, NurseP (1991) Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol 194: 795–823.
56. CastilloEA, AyteJ, ChivaC, MoldonA, CarrascalM, et al. (2002) Diethylmaleate activates the transcription factor Pap1 by covalent modification of critical cysteine residues. Mol Microbiol 45: 243–254.
57. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
58. BjorkGR, JacobssonK, NilssonK, JohanssonMJ, BystromAS, et al. (2001) A primordial tRNA modification required for the evolution of life? Embo J 20: 231–239.
59. LauNC, LimLP, WeinsteinEG, BartelDP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294: 858–862.
60. SmithGR (2009) Genetic analysis of meiotic recombination in Schizosaccharomyces pombe. Methods Mol Biol 557: 65–76.
61. WoodV, HarrisMA, McDowallMD, RutherfordK, VaughanBW, et al. (2012) PomBase: a comprehensive online resource for fission yeast. Nucleic Acids Res 40: D695–699.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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