Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification

English version České info

Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5-carbamoylmethyluridine (ncm⁵U₃₄), 5-methoxycarbonylmethyluridine (mcm⁵U₃₄), and 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U₃₄) at wobble position in tRNA. These modified nucleosides are important for efficient decoding during translation. In a recent publication, Elongator complex was implicated to participate in telomeric gene silencing and DNA damage response by interacting with proliferating cell nuclear antigen (PCNA). Here we show that elevated levels of tRNA^Lys_s²_UUU, tRNA^Gln_s²_UUG, and tRNA^Glu_s²_UUC, which in a wild-type background contain the mcm⁵s²U nucleoside at position 34, suppress the defects in telomeric gene silencing and DNA damage response observed in the Elongator mutants. We also found that the reported differences in telomeric gene silencing and DNA damage response of various elp3 alleles correlated with the levels of modified nucleosides at U₃₄. Defects in telomeric gene silencing and DNA damage response are also observed in strains with the tuc2Δ mutation, which abolish the formation of the 2-thio group of the mcm⁵s²U nucleoside in tRNA^Lys_{mcm⁵_s²_UUU}, tRNA^Gln_{mcm⁵_s²_UUG}, and tRNA^Glu_{mcm⁵_s²_UUC}. These observations show that Elongator complex does not directly participate in telomeric gene silencing and DNA damage response, but rather that modified nucleosides at U₃₄ are important for efficient expression of gene products involved in these processes. Consistent with this notion, we found that expression of Sir4, a silent information regulator required for assembly of silent chromatin at telomeres, was decreased in the elp3Δ mutants.

Vyšlo v časopise: Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification. PLoS Genet 7(9): e32767. doi:10.1371/journal.pgen.1002258
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002258

Souhrn

Zdroje

1. OteroGFellowsJLiYde BizemontTDiracAM 1999 Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol Cell 3 109 118

2. WinklerGSPetrakisTGEthelbergSTokunagaMErdjument-BromageH 2001 RNA polymerase II elongator holoenzyme is composed of two discrete subcomplexes. J Biol Chem 276 32743 32749

3. KroganNJGreenblattJF 2001 Characterization of a six-subunit holo-elongator complex required for the regulated expression of a group of genes in Saccharomyces cerevisiae. Mol Cell Biol 21 8203 8212

4. HawkesNAOteroGWinklerGSMarshallNDahmusME 2002 Purification and characterization of the human elongator complex. J Biol Chem 277 3047 3052

5. KimJHLaneWSReinbergD 2002 Human Elongator facilitates RNA polymerase II transcription through chromatin. Proc Natl Acad Sci U S A 99 1241 1246

6. WittschiebenBOOteroGde BizemontTFellowsJErdjument-BromageH 1999 A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme. Mol Cell 4 123 128

7. WinklerGSKristjuhanAErdjument-BromageHTempstPSvejstrupJQ 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

8. RahlPBChenCZCollinsRN 2005 Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation. Mol Cell 17 841 853

9. FrohloffFFichtnerLJablonowskiDBreunigKDSchaffrathR 2001 Saccharomyces cerevisiae Elongator mutations confer resistance to the Kluyveromyces lactis zymocin. EMBO J 20 1993 2003

10. HuangBJohanssonMJByströmAS 2005 An early step in wobble uridine tRNA modification requires the Elongator complex. RNA 11 424 436

11. LuJHuangBEsbergAJohanssonMJByströmAS 2005 The Kluyveromyces lactis gamma-toxin targets tRNA anticodons. RNA 11 1648 1654

12. JohanssonMJEsbergAHuangBBjörkGRByströmAS 2008 Eukaryotic wobble uridine modifications promote a functionally redundant decoding system. Mol Cell Biol

13. ChenCTuckSByströmAS 2009 Defects in tRNA modification associated with neurological and developmental dysfunctions in Caenorhabditis elegans elongator mutants. PLoS Genet 5 e1000561 doi:10.1371/journal.pgen.1000561

14. MehlgartenCJablonowskiDWrackmeyerUTschitschmannSSondermannD 2010 Elongator function in tRNA wobble uridine modification is conserved between yeast and plants. Mol Microbiol 76 1082 1094

15. EsbergAHuangBJohanssonMJByströmAS 2006 Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Mol Cell 24 139 148

16. CamposEIReinbergD 2009 Histones: annotating chromatin. Annu Rev Genet 43 559 599

17. ClapierCRCairnsBR 2009 The biology of chromatin remodeling complexes. Annu Rev Biochem 78 273 304

18. SofiaHJChenGHetzlerBGReyes-SpindolaJFMillerNE 2001 Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods. Nucleic Acids Res 29 1097 1106

19. LiQFazlyAMZhouHHuangSZhangZ 2009 The elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to DNA damage agents. PLoS Genet 5 e1000684 doi:10.1371/journal.pgen.1000684

20. GottschlingDEAparicioOMBillingtonBLZakianVA 1990 Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 63 751 762

21. FillinghamJRechtJSilvaACSuterBEmiliA 2008 Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109. Mol Cell Biol 28 4342 4353

22. LinLJMinardLVJohnstonGCSingerRASchultzMC 2010 Asf1 can promote trimethylation of H3 K36 by Set2. Mol Cell Biol 30 1116 1129

23. TsubotaTBerndsenCEErkmannJASmithCLYangL 2007 Histone H3-K56 acetylation is catalyzed by histone chaperone-dependent complexes. Mol Cell 25 703 712

24. GrantPADugganLCoteJRobertsSMBrownellJE 1997 Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex. Genes Dev 11 1640 1650

25. EberharterASternerDESchieltzDHassanAYatesJR3rd 1999 The ADA complex is a distinct histone acetyltransferase complex in Saccharomyces cerevisiae. Mol Cell Biol 19 6621 6631

26. WittschiebenBOFellowsJDuWStillmanDJSvejstrupJQ 2000 Overlapping roles for the histone acetyltransferase activities of SAGA and elongator in vivo. EMBO J 19 3060 3068

27. KeelingKMLanierJDuMSalas-MarcoJGaoL 2004 Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae. RNA 10 691 703

28. BjörkGRHuangBPerssonOPByströmAS 2007 A conserved modified wobble nucleoside (mcm5s2U) in lysyl-tRNA is required for viability in yeast. RNA 13 1245 1255

29. PokholokDKHannettNMYoungRA 2002 Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell 9 799 809

30. HuhWKFalvoJVGerkeLCCarrollASHowsonRW 2003 Global analysis of protein localization in budding yeast. Nature 425 686 691

31. BegleyUDyavaiahMPatilARooneyJPDiRenzoD 2007 Trm9-catalyzed tRNA modifications link translation to the DNA damage response. Mol Cell 28 860 870

32. ClosePHawkesNCornezICreppeCLambertCA 2006 Transcription impairment and cell migration defects in elongator-depleted cells: implication for familial dysautonomia. Mol Cell 22 521 531

33. HolmbergCKatzSLerdrupMHerdegenTJaattelaM 2002 A novel specific role for I kappa B kinase complex-associated protein in cytosolic stress signaling. J Biol Chem 277 31918 31928

34. NelissenHFleuryDBrunoLRoblesPDe VeylderL 2005 The elongata mutants identify a functional Elongator complex in plants with a role in cell proliferation during organ growth. Proc Natl Acad Sci U S A 102 7754 7759

35. CreppeCMalinouskayaLVolvertMLGillardMCloseP 2009 Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin. Cell 136 551 564

36. SolingerJAPaolinelliRKlossHScorzaFBMarchesiS 2010 The Caenorhabditis elegans Elongator complex regulates neuronal alpha-tubulin acetylation. PLoS Genet 6 e1000820 doi:10.1371/journal.pgen.1000820

37. AkellaJSWlogaDKimJStarostinaNGLyons-AbbottS 2010 MEC-17 is an alpha-tubulin acetyltransferase. Nature 467 218 222

38. ParaskevopoulouCFairhurstSALoweDJBrickPOnestiS 2006 The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine. Mol Microbiol 59 795 806

39. GreenwoodCSelthLADirac-SvejstrupABSvejstrupJQ 2009 An iron-sulfur cluster domain in Elp3 important for the structural integrity of elongator. J Biol Chem 284 141 149

40. BurkeDDawsonDStearnsT 2000 Methods in Yeast Genetics Cold Spring Harbor, NY Cold Spring Harbor Laboratory Press

41. BjörkGRJacobssonKNilssonKJohanssonMJByströmAS 2001 A primordial tRNA modification required for the evolution of life? EMBO J 20 231 239

42. HeFAmraniNJohanssonMJJacobsonA 2008 Chapter 6. Qualitative and quantitative assessment of the activity of the yeast nonsense-mediated mRNA decay pathway. Methods Enzymol 449 127 147

43. FiorentiniPHuangKNTishkoffDXKolodnerRDSymingtonLS 1997 Exonuclease I of Saccharomyces cerevisiae functions in mitotic recombination in vivo and in vitro. Mol Cell Biol 17 2764 2773

44. SikorskiRSHieterP 1989 A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122 19 27

45. ChristiansonTWSikorskiRSDanteMSheroJHHieterP 1992 Multifunctional yeast high-copy-number shuttle vectors. Gene 110 119 122