Transcriptome Kinetics Is Governed by a Genome-Wide Coupling of mRNA Production and Degradation: A Role for RNA Pol II
Transcriptome dynamics is governed by two opposing processes, mRNA production and degradation. Recent studies found that changes in these processes are frequently coordinated and that the relationship between them shapes transcriptome kinetics. Specifically, when transcription changes are counter-acted with changes in mRNA stability, transient fast-relaxing transcriptome kinetics is observed. A possible molecular mechanism underlying such coordinated regulation might lay in two RNA polymerase (Pol II) subunits, Rpb4 and Rpb7, which are recruited to mRNAs during transcription and later affect their degradation in the cytoplasm. Here we used a yeast strain carrying a mutant Pol II which poorly recruits these subunits. We show that this mutant strain is impaired in its ability to modulate mRNA stability in response to stress. The normal negative coordinated regulation is lost in the mutant, resulting in abnormal transcriptome profiles both with respect to magnitude and kinetics of responses. These results reveal an important role for Pol II, in regulation of both mRNA synthesis and degradation, and also in coordinating between them. We propose a simple model for production-degradation coupling that accounts for our observations. The model shows how a simple manipulation of the rates of co-transcriptional mRNA imprinting by Pol II may govern genome-wide transcriptome kinetics in response to environmental changes.
Vyšlo v časopise:
Transcriptome Kinetics Is Governed by a Genome-Wide Coupling of mRNA Production and Degradation: A Role for RNA Pol II. PLoS Genet 7(9): e32767. doi:10.1371/journal.pgen.1002273
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002273
Souhrn
Transcriptome dynamics is governed by two opposing processes, mRNA production and degradation. Recent studies found that changes in these processes are frequently coordinated and that the relationship between them shapes transcriptome kinetics. Specifically, when transcription changes are counter-acted with changes in mRNA stability, transient fast-relaxing transcriptome kinetics is observed. A possible molecular mechanism underlying such coordinated regulation might lay in two RNA polymerase (Pol II) subunits, Rpb4 and Rpb7, which are recruited to mRNAs during transcription and later affect their degradation in the cytoplasm. Here we used a yeast strain carrying a mutant Pol II which poorly recruits these subunits. We show that this mutant strain is impaired in its ability to modulate mRNA stability in response to stress. The normal negative coordinated regulation is lost in the mutant, resulting in abnormal transcriptome profiles both with respect to magnitude and kinetics of responses. These results reveal an important role for Pol II, in regulation of both mRNA synthesis and degradation, and also in coordinating between them. We propose a simple model for production-degradation coupling that accounts for our observations. The model shows how a simple manipulation of the rates of co-transcriptional mRNA imprinting by Pol II may govern genome-wide transcriptome kinetics in response to environmental changes.
Zdroje
1. GrigullJMnaimnehSPootoolalJRobinsonMDHughesTR 2004 Genome-wide analysis of mRNA stability using transcription inhibitors and microarrays reveals posttranscriptional control of ribosome biogenesis factors. Molecular and cellular biology 24 5534 47
2. WangYLiuCLStoreyJDTibshiraniRJHerschlagD 2002 Precision and functional specificity in mRNA decay. Proceedings of the National Academy of Sciences of the United States of America 99 5860 5
3. BernsteinJAKhodurskyABLinP-HLin-ChaoSCohenSN 2002 Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays. Proceedings of the National Academy of Sciences of the United States of America 99 9697 702
4. NarsaiRHowellKAMillarAHO'TooleNSmallI 2007 Genome-wide analysis of mRNA decay rates and their determinants in Arabidopsis thaliana. The Plant cell 19 3418 36
5. García-MartínezJArandaAPérez-OrtínJE 2004 Genomic run-on evaluates transcription rates for all yeast genes and identifies gene regulatory mechanisms. Molecular cell 15 303 13
6. PelechanoVChávezSPérez-OrtínJE 2010 A complete set of nascent transcription rates for yeast genes. PloS ONE 5 e15442 doi:10.1371/journal.pone.0015442
7. MillerCSchwalbBMaierKSchulzDDümckeS 2011 Dynamic transcriptome analysis measures rates of mRNA synthesis and decay in yeast. Molecular systems biology 7 458
8. Molina-NavarroMMCastells-RocaLBellíGGarcía-MartínezJMarín-NavarroJ 2008 Comprehensive transcriptional analysis of the oxidative response in yeast. The Journal of biological chemistry 283 17908 18
9. ShalemODahanOLevoMMartinezMRFurmanI 2008 Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradation. Molecular systems biology 4 223
10. MolinCJauhiainenAWarringerJNermanOSunnerhagenP 2009 mRNA stability changes precede changes in steady-state mRNA amounts during hyperosmotic stress. RNA (New York, N.Y.) 15 600 14
11. FanJYangXWangWWoodWHBeckerKG 2002 Global analysis of stress-regulated mRNA turnover by using cDNA arrays. Proceedings of the National Academy of Sciences of the United States of America 99 10611 6
12. FoatBCHoushmandiSSOlivasWMBussemakerHJ 2005 Profiling condition-specific, genome-wide regulation of mRNA stability in yeast. Proceedings of the National Academy of Sciences of the United States of America 102 17675 80
13. AmorimMJCotobalCDuncanCMataJ 2010 Global coordination of transcriptional control and mRNA decay during cellular differentiation. Molecular systems biology 6 380
14. ElkonRZlotorynskiEZellerKIAgamiR 2010 Major role for mRNA stability in shaping the kinetics of gene induction. BMC genomics 11 259
15. Pérez-OrtínJEAlepuzPMMorenoJ 2007 Genomics and gene transcription kinetics in yeast. Trends in genetics: TIG 23 250 7
16. Romero-SantacreuLMorenoJPérez-OrtínJEAlepuzP 2009 Specific and global regulation of mRNA stability during osmotic stress in Saccharomyces cerevisiae. RNA (New York, N.Y.) 15 1110 20
17. JasiakAJHartmannHKarakasiliEKalocsayMFlatleyA 2008 Genome-associated RNA polymerase II includes the dissociable Rpb4/7 subcomplex. The Journal of biological chemistry 283 26423 7
18. PillaiBVermaJAbrahamAFrancisPKumarY 2003 Whole genome expression profiles of yeast RNA polymerase II core subunit, Rpb4, in stress and nonstress conditions. The Journal of biological chemistry 278 3339 46
19. Goler-BaronVSelitrennikMBarkaiOHaimovichGLotanR 2008 Transcription in the nucleus and mRNA decay in the cytoplasm are coupled processes. Genes & development 22 2022 7
20. LotanRBar-OnVGHarel-SharvitLDuekLMelamedD 2005 The RNA polymerase II subunit Rpb4p mediates decay of a specific class of mRNAs. Genes & development 19 3004 16
21. LotanRGoler-BaronVDuekLHaimovichGChoderM 2007 The Rpb7p subunit of yeast RNA polymerase II plays roles in the two major cytoplasmic mRNA decay mechanisms. The Journal of cell biology 178 1133 43
22. Harel-SharvitLEldadNHaimovichGBarkaiODuekL 2010 RNA polymerase II subunits link transcription and mRNA decay to translation. Cell 143 552 63
23. BushnellDAKornbergRD 2003 Complete, 12-subunit RNA polymerase II at 4.1-A resolution: implications for the initiation of transcription. Proceedings of the National Academy of Sciences of the United States of America 100 6969 73
24. UjváriALuseDS 2006 RNA emerging from the active site of RNA polymerase II interacts with the Rpb7 subunit. Nature structural & molecular biology 13 49 54
25. RunnerVMPodolnyVBuratowskiS 2008 The Rpb4 subunit of RNA polymerase II contributes to cotranscriptional recruitment of 3′ processing factors. Molecular and cellular biology 28 1883 91
26. TanQPrysakMHWoychikNA 2003 Loss of the Rpb4/Rpb7 subcomplex in a mutant form of the Rpb6 subunit shared by RNA polymerases I, II, and III. Molecular and cellular biology 23 3329 38
27. ShefferAVaronMChoderM 1999 Rpb7 can interact with RNA polymerase II and support transcription during some stresses independently of Rpb4. Molecular and cellular biology 19 2672 80
28. ChoderM 2011 mRNA imprinting: Additional level in the regulation of gene expression. Cellular logistics 1 37 40
29. SelitrennikMDuekLLotanRChoderM 2006 Nucleocytoplasmic shuttling of the Rpb4p and Rpb7p subunits of Saccharomyces cerevisiae RNA polymerase II by two pathways. Eukaryotic cell 5 2092 103
30. FaragoMNahariTHammelCColeCNChoderM 2003 Rpb4p, a subunit of RNA polymerase II, mediates mRNA export during stress. Molecular biology of the cell 14 2744 55
31. HalbeisenREGerberAP 2009 Stress-Dependent Coordination of Transcriptome and Translatome in Yeast. PLoS Biol 7 e1000105 doi:10.1371/journal.pbio.1000105
32. ProshkinSRahmouniARMironovANudlerE 2010 Cooperation between translating ribosomes and RNA polymerase in transcription elongation. Science (New York, N.Y.) 328 504 8
33. ShenZSt-DenisAChartrandP 2010 Cotranscriptional recruitment of She2p by RNA pol II elongation factor Spt4-Spt5/DSIF promotes mRNA localization to the yeast bud. Genes & development 24 1914 26
34. Dori-BachashMShemaETiroshI 2011 Coupled Evolution of Transcription and mRNA Degradation. PLoS Biol 9 e1001106 doi:10.1371/journal.pbio.1001106
35. ShalgiRLieberDOrenMPilpelY 2007 Global and local architecture of the mammalian microRNA-transcription factor regulatory network. PLoS Comp Biol 3 e131 doi:10.1371/journal.pcbi.0030131
36. TsangJSEbertMSvan OudenaardenA 2010 Genome-wide dissection of microRNA functions and cotargeting networks using gene set signatures. Molecular cell 38 140 53
37. AvrahamRSas-ChenAManorOSteinfeldIShalgiR 2010 EGF decreases the abundance of microRNAs that restrain oncogenic transcription factors. Science signaling 3 ra43
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 9
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