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TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast.
- Source :
-
Molecular cell [Mol Cell] 2009 Mar 27; Vol. 33 (6), pp. 738-51. - Publication Year :
- 2009
-
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.
- Subjects :
- Chromosomal Proteins, Non-Histone genetics
Chromosomal Proteins, Non-Histone metabolism
Cyclin-Dependent Kinase 9 antagonists & inhibitors
Cyclin-Dependent Kinase 9 genetics
Cyclin-Dependent Kinase 9 metabolism
Cyclin-Dependent Kinases antagonists & inhibitors
Cyclin-Dependent Kinases genetics
Cyclin-Dependent Kinases metabolism
Methyltransferases genetics
Methyltransferases metabolism
Mutation genetics
Oligonucleotide Array Sequence Analysis
Phosphorylation
Positive Transcriptional Elongation Factor B metabolism
Protein Kinases genetics
Protein Kinases metabolism
RNA Polymerase II genetics
RNA Polymerase II metabolism
Reverse Transcriptase Polymerase Chain Reaction
Schizosaccharomyces genetics
Schizosaccharomyces growth & development
Schizosaccharomyces pombe Proteins genetics
Schizosaccharomyces pombe Proteins metabolism
Transcription Factor TFIIH metabolism
Transcriptional Elongation Factors genetics
Transcriptional Elongation Factors metabolism
Cyclin-Dependent Kinase-Activating Kinase
Positive Transcriptional Elongation Factor B genetics
RNA Caps genetics
Schizosaccharomyces metabolism
Transcription Factor TFIIH genetics
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 33
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 19328067
- Full Text :
- https://doi.org/10.1016/j.molcel.2009.01.029