Gene-specific RNA polymerase II phosphorylation and the CTD code.
Phosphorylation of the RNA polymerase (Pol) II C-terminal domain (CTD) repeats (1-YSPTSPS-7) is coupled to transcription and may act as a 'code' that controls mRNA synthesis and processing. To examine the code in budding yeast, we mapped genome-wide CTD Ser2, Ser5 and Ser7 phosphorylations and the CTD-associated termination factors Nrd1 and Pcf11. Phospho-CTD dynamics are not scaled to gene length and are gene-specific, with highest Ser5 and Ser7 phosphorylation at the 5' ends of well-expressed genes with nucleosome-occupied promoters. The CTD kinases Kin28 and Ctk1 markedly affect Pol II distribution in a gene-specific way. The code is therefore written differently on different genes, probably under the control of promoters. Ser7 phosphorylation is enriched on introns and at sites of Nrd1 accumulation, suggesting links to splicing and Nrd1 recruitment. Nrd1 and Pcf11 frequently colocalize, suggesting functional overlap. Unexpectedly, Pcf11 is enriched at centromeres and Pol III-transcribed genes.
Kim
Hyunmin
H
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Erickson
Benjamin
B
Luo
Weifei
W
Seward
David
D
Graber
Joel H
JH
Pollock
David D
DD
Megee
Paul C
PC
Bentley
David L
DL
D047369:Chromatin Immunoprecipitation; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000502:physiology; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D055106:Genome-Wide Association Study; D007438:Introns / Q000235:genetics; D046911:Macromolecular Substances; D008957:Models, Genetic; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
D004271:DNA, Fungal; D046911:Macromolecular Substances; C491211:NRD1 protein, S cerevisiae; C512637:PCF11 protein, S cerevisiae; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D010768:Phosphoserine; D011494:Protein Kinases; C060137:carboxy-terminal domain kinase; D018844:Cyclin-Dependent Kinases; C084210:Kin28 protein kinase, S cerevisiae; D012319:RNA Polymerase II; C112110:RPB3 protein, S cerevisiae