Cryptic Transcription Mediates Repression of Subtelomeric Metal Homeostasis Genes

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Nonsense-mediated mRNA decay (NMD) prevents the accumulation of transcripts bearing premature termination codons. Here we show that Saccharomyces cerevisiae NMD mutants accumulate 5′–extended RNAs (CD-CUTs) of many subtelomeric genes. Using the subtelomeric ZRT1 and FIT3 genes activated in response to zinc and iron deficiency, respectively, we show that transcription of these CD-CUTs mediates repression at the bona fide promoters, by preventing premature binding of RNA polymerase II in conditions of metal repletion. Expression of the main ZRT1 CD-CUT is controlled by the histone deacetylase Rpd3p, showing that histone deacetylases can regulate expression of genes through modulation of the level of CD-CUTs. Analysis of binding of the transcriptional activator Zap1p and insertion of transcriptional terminators upstream from the Zap1p binding sites show that CD-CUT transcription or accumulation also interferes with binding of the transcriptional activator Zap1p. Consistent with this model, overexpressing Zap1p or using a constitutively active version of the Aft1p transcriptional activator rescues the induction defect of ZRT1 and FIT3 in NMD mutants. These results show that cryptic upstream sense transcription resulting in unstable transcripts degraded by NMD controls repression of a large number of genes located in subtelomeric regions, and in particular of many metal homeostasis genes.

Vyšlo v časopise: Cryptic Transcription Mediates Repression of Subtelomeric Metal Homeostasis Genes. PLoS Genet 7(6): e32767. doi:10.1371/journal.pgen.1002163
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002163

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Zdroje

1. JacquierA 2009 The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat Rev Genet 10 833 844

2. NeilHMalabatCd'Aubenton-CarafaYXuZSteinmetzLM 2009 Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 457 1038 1042

3. MartensJALapradeLWinstonF 2004 Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene. Nature 429 571 574

4. CamblongJIglesiasNFickentscherCDieppoisGStutzF 2007 Antisense RNA stabilization induces transcriptional gene silencing via histone deacetylation in S. cerevisiae. Cell 131 706 717

5. BerrettaJPinskayaMMorillonA 2008 A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae. Genes Dev 22 615 626

6. HouseleyJRubbiLGrunsteinMTollerveyDVogelauerM 2008 A ncRNA modulates histone modification and mRNA induction in the yeast GAL gene cluster. Mol Cell 32 685 695

7. CamblongJBeyrouthyNGuffantiESchlaepferGSteinmetzLM 2009 Trans-acting antisense RNAs mediate transcriptional gene cosuppression in S. cerevisiae. Genes Dev 23 1534 1545

8. BumgarnerSLDowellRDGrisafiPGiffordDKFinkGR 2009 Toggle involving cis-interfering noncoding RNAs controls variegated gene expression in yeast. Proc Natl Acad Sci U S A 106 18321 18326

9. XuZWeiWGagneurJPerocchiFClauder-MunsterS 2009 Bidirectional promoters generate pervasive transcription in yeast. Nature 457 1033 1037

10. KimTKHembergMGrayJMCostaAMBearDM 2010 Widespread transcription at neuronal activity-regulated enhancers. Nature 465 182 187

11. WyersFRougemailleMBadisGRousselleJCDufourME 2005 Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121 725 737

12. LeeAHansenKDBullardJDudoitSSherlockG 2008 Novel low abundance and transient RNAs in yeast revealed by tiling microarrays and ultra high-throughput sequencing are not conserved across closely related yeast species. PLoS Genet 4 e1000299 doi:10.1371/journal.pgen.1000299

13. ThompsonDMParkerR 2007 Cytoplasmic decay of intergenic transcripts in Saccharomyces cerevisiae. Mol Cell Biol 27 92 101

14. ChangYFImamJSWilkinsonMF 2007 The Nonsense-Mediated Decay RNA Surveillance Pathway. Annu Rev Biochem 76 51 74

15. IskenOMaquatLE 2007 Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev 21 1833 1856

16. FrischmeyerPADietzHC 1999 Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet 8 1893 1900

17. KuzmiakHAMaquatLE 2006 Applying nonsense-mediated mRNA decay research to the clinic: progress and challenges. Trends Mol Med 12 306 316

18. MitrovichQMAndersonP 2000 Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans. Genes Dev 14 2173 2184

19. LareauLFInadaMGreenREWengrodJCBrennerSE 2007 Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements. Nature 446 926 929

20. NiJZGrateLDonohueJPPrestonCNobidaN 2007 Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay. Genes Dev 21 708 718

21. SayaniSJanisMLeeCYToescaIChanfreauGF 2008 Widespread impact of nonsense-mediated mRNA decay on the yeast intronome. Mol Cell 31 360 370

22. KebaaraBWAtkinAL 2009 Long 3′-UTRs target wild-type mRNAs for nonsense-mediated mRNA decay in Saccharomyces cerevisiae. Nucleic Acids Res 37 2771 2778

23. JohanssonMJJacobsonA 2010 Nonsense-mediated mRNA decay maintains translational fidelity by limiting magnesium uptake. Genes Dev 24 1491 1495

24. LeliveltMJCulbertsonMR 1999 Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome. Mol Cell Biol 19 6710 6719

25. HeFLiXSpatrickPCasilloRDongS 2003 Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5′ to 3′ mRNA decay pathways in yeast. Mol Cell 12 1439 1452

26. GuanQZhengWTangSLiuXZinkelRA 2006 Impact of nonsense-mediated mRNA decay on the global expression profile of budding yeast. PLoS Genet 2 e203 doi:10.1371/journal.pgen.0020203

27. JohanssonMJHeFSpatrickPLiCJacobsonA 2007 Association of yeast Upf1p with direct substrates of the NMD pathway. Proc Natl Acad Sci U S A 104 20872 20877

28. LyonsTJGaschAPGaitherLABotsteinDBrownPO 2000 Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. Proc Natl Acad Sci U S A 97 7957 7962

29. ProtchenkoOFereaTRashfordJTiedemanJBrownPO 2001 Three cell wall mannoproteins facilitate the uptake of iron in Saccharomyces cerevisiae. J Biol Chem 276 49244 49250

30. RobyrDSukaYXenariosIKurdistaniSKWangA 2002 Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell 109 437 446

31. LeeAHenrasAKChanfreauG 2005 Multiple RNA surveillance pathways limit aberrant expression of iron uptake mRNAs and prevent iron toxicity in S. cerevisiae. Mol Cell 19 39 51

32. MartianovIRamadassASerra BarrosAChowNAkoulitchevA 2007 Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature 445 666 670

33. WangXAraiSSongXReichartDDuK 2008 Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature

34. ZhaoHEideD 1996 The ZRT2 gene encodes the low affinity zinc transporter in Saccharomyces cerevisiae. J Biol Chem 271 23203 23210

35. TaylorRKebaaraBWNazarenusTJonesAYamanakaR 2005 Gene set coregulated by the Saccharomyces cerevisiae nonsense-mediated mRNA decay pathway. Eukaryot Cell 4 2066 2077

36. LongtineMSMcKenzieA3rdDemariniDJShahNGWachA 1998 Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14 953 961

37. BernsteinBETongJKSchreiberSL 2000 Genomewide studies of histone deacetylase function in yeast. Proc Natl Acad Sci U S A 97 13708 13713

38. ZhaoHButlerERodgersJSpizzoTDuesterhoeftS 1998 Regulation of zinc homeostasis in yeast by binding of the ZAP1 transcriptional activator to zinc-responsive promoter elements. J Biol Chem 273 28713 28720

39. Yamaguchi-IwaiYDancisAKlausnerRD 1995 AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae. EMBO J 14 1231 1239

40. PhilpottCCRashfordJYamaguchi-IwaiYRouaultTADancisA 1998 Cell-cycle arrest and inhibition of G1 cyclin translation by iron in AFT1-1(up) yeast. EMBO J 17 5026 5036

41. van de PeppelJKettelarijNvan BakelHKockelkornTTvan LeenenD 2005 Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets. Mol Cell 19 511 522

42. BertonePStolcVRoyceTERozowskyJSUrbanAE 2004 Global identification of human transcribed sequences with genome tiling arrays. Science 306 2242 2246

43. KapranovPChengJDikeSNixDADuttaguptaR 2007 RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316 1484 1488

44. NagalakshmiUWangZWaernKShouCRahaD 2008 The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 320 1344 1349

45. AmraniNDongSHeFGanesanRGhoshS 2006 Aberrant termination triggers nonsense-mediated mRNA decay. Biochem Soc Trans 34 39 42

46. DavisCAAresMJr 2006 Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 103 3262 3267

47. ChekanovaJAGregoryBDReverdattoSVChenHKumarR 2007 Genome-wide high-resolution mapping of exosome substrates reveals hidden features in the Arabidopsis transcriptome. Cell 131 1340 1353

48. GrundSEFischerTCabalGGAntunezOPerez-OrtinJE 2008 The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression. J Cell Biol 182 897 910

49. DieppoisGStutzF 2010 Connecting the transcription site to the nuclear pore: a multi-tether process that regulates gene expression. J Cell Sci 123 1989 1999

50. NazarenusTCedarbergRBellRCheatleJForchA 2005 Upf1p, a highly conserved protein required for nonsense-mediated mRNA decay, interacts with the nuclear pore proteins Nup100p and Nup116p. Gene 345 199 212

51. BirdAJGordonMEideDJWingeDR 2006 Repression of ADH1 and ADH3 during zinc deficiency by Zap1-induced intergenic RNA transcripts. EMBO J 25 5726 5734

52. MoseleyJLPageMDAlderNPErikssonMQuinnJ 2002 Reciprocal expression of two candidate di-iron enzymes affecting photosystem I and light-harvesting complex accumulation. Plant Cell 14 673 688

53. StoriciFLewisLKResnickMA 2001 In vivo site-directed mutagenesis using oligonucleotides. Nat Biotechnol 19 773 776

54. YangPKHoareauCFromentCMonsarratBHenryY 2005 Cotranscriptional recruitment of the pseudouridylsynthetase Cbf5p and of the RNA binding protein Naf1p during H/ACA snoRNP assembly. Mol Cell Biol 25 3295 3304

55. SteinmetzEJWarrenCLKuehnerJNPanbehiBAnsariAZ 2006 Genome-wide distribution of yeast RNA polymerase II and its control by Sen1 helicase. Mol Cell 24 735 746