TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast Journal Article

Authors: Viladevall, L.; St. Amour, C. V.; Rosebrock, A.; Schneider, S.; Zhang, C.; Allen, J. J.; Shokat, K. M.; Schwer, B.; Leatherwood, J. K.; Fisher, R. P.
Article Title: TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast
Abstract: Cyclin-dependent kinases (CDKs) are subunits of transcription factor (TF) IIH and positive transcription elongation factor b (P-TEFb). To define their functions, we mutated the TFIIH-associated kinase Mcs6 and P-TEFb homologs Cdk9 and Lsk1 of fission yeast, making them sensitive to inhibition by bulky purine analogs. Selective inhibition of Mcs6 or Cdk9 blocks cell division, alters RNA polymerase (Pol) II carboxyl-terminal domain (CTD) phosphorylation, and represses specific, overlapping subsets of transcripts. At a common target gene, both CDKs must be active for normal Pol II occupancy, and Spt5-a CDK substrate and regulator of elongation-accumulates disproportionately to Pol II when either kinase is inhibited. In contrast, Mcs6 activity is sufficient-and necessary-to recruit the Cdk9/Pcm1 (mRNA cap methyltransferase) complex. In vitro, phosphorylation of the CTD by Mcs6 stimulates subsequent phosphorylation by Cdk9. We propose that TFIIH primes the CTD and promotes recruitment of P-TEFb/Pcm1, serving to couple elongation and capping of select pre-mRNAs. © 2009 Elsevier Inc. All rights reserved.
Keywords: controlled study; protein expression; protein phosphorylation; unclassified drug; mutation; nonhuman; protein domain; protein function; proteins; chromosomal proteins, non-histone; cell division; protein kinases; cyclin dependent kinase 9; transcription, genetic; in vitro study; mutational analysis; phosphorylation; rna; methyltransferases; dna; reverse transcriptase polymerase chain reaction; rna caps; oligonucleotide array sequence analysis; chromatin immunoprecipitation; cyclin-dependent kinases; rna polymerase ii; schizosaccharomyces; schizosaccharomyces pombe proteins; schizosaccharomycetaceae; cyclin dependent kinase 1; transcriptional elongation factors; elongation factor; positive transcription factor elongation factor b; protein mcs6; transcription factor iih; cyclin-dependent kinase 9; positive transcriptional elongation factor b; transcription factor tfiih
Journal Title: Molecular Cell
Volume: 33
Issue: 6
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2009-03-27
Start Page: 738
End Page: 751
Language: English
DOI: 10.1016/j.molcel.2009.01.029
PUBMED: 19328067
PROVIDER: scopus
PMCID: PMC2693121
Notes: --- - "Cited By (since 1996): 14" - "Export Date: 30 November 2010" - "CODEN: MOCEF" - "Source: Scopus"
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MSK Authors
  1. Robert P Fisher
    28 Fisher