Dephosphorylation of RNA polymerase II by CTD-phosphatase FCP1 is inhibited by phospho-CTD associating proteins.
Reversible phosphorylation of the repetitive C-terminal domain (CTD) of the largest RNA polymerase (RNAP) II subunit plays a key role in the progression of RNAP through the transcription cycle. The level of CTD phosphorylation is determined by multiple CTD kinases and a CTD phosphatase, FCP1. The phosphorylated CTD binds to a variety of proteins including the cis/trans peptidyl-prolyl isomerase (PPIase) Pin1 and enzymes involved in processing of the primary transcript such as the capping enzyme Hce1 and CA150, a nuclear factor implicated in transcription elongation. Results presented here establish that the dephosphorylation of hyperphosphorylated RNAP II (RNAP IIO) by FCP1 is impaired in the presence of Pin1 or Hce1, whereas CA150 has no influence on FCP1 activity. The inhibition of dephosphorylation is observed with free RNAP IIO generated by different CTD kinases as well as with RNAP IIO engaged in an elongation complex. These findings support the idea that specific phospho-CTD associating proteins can differentially modulate the dephosphorylation of RNAP IIO by steric hindrance and may play an important role in the regulation of gene expression.
Palancade
Benoît
B
Génétique Moléculaire, UMR 8541 CNRS, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
Marshall
Nicholas F
NF
Tremeau-Bravard
Alexandre
A
Bensaude
Olivier
O
Dahmus
Michael E
ME
Dubois
Marie-Françoise
MF
D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009713:Nucleotidyltransferases / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D035602:Transcriptional Elongation Factors; D000098556:mRNA Guanylyltransferases
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C108440:TCERG1 protein, human; D015534:Trans-Activators; D035602:Transcriptional Elongation Factors; D009713:Nucleotidyltransferases; D012319:RNA Polymerase II; D000098556:mRNA Guanylyltransferases; D010749:Phosphoprotein Phosphatases; C116022:carboxy-terminal domain phosphatase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase