title: A universal RNA polymerase II CTD cycle is orchestrated by complex interplays between kinase, phosphatase, and isomerase enzymes along genes.
abstract: Transcription by RNA polymerase II (RNAPII) is coupled to mRNA processing and chromatin modifications via the C-terminal domain (CTD) of its largest subunit, consisting of multiple repeats of the heptapeptide YSPTSPS. Pioneering studies showed that CTD serines are differentially phosphorylated along genes in a prescribed pattern during the transcription cycle. Genome-wide analyses challenged this idea, suggesting that this cycle is not uniform among different genes. Moreover, the respective role of enzymes responsible for CTD modifications remains controversial. Here, we systematically profiled the location of the RNAPII phosphoisoforms in wild-type cells and mutants for most CTD modifying enzymes. Together with results of in vitro assays, these data reveal a complex interplay between the modifying enzymes, and provide evidence that the CTD cycle is uniform across genes. We also identify Ssu72 as the Ser7 phosphatase and show that proline isomerization is a key regulator of CTD dephosphorylation at the end of genes.
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
authors.forename: Alain R
authors.initials: AR
authors.lastname: Bataille
authors.forename: Célia
authors.initials: C
authors.lastname: Jeronimo
authors.forename: Pierre-Étienne
authors.initials: PÉ
authors.lastname: Jacques
authors.forename: Louise
authors.initials: L
authors.lastname: Laramée
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Fortin
authors.forename: Audrey
authors.initials: A
authors.lastname: Forest
authors.forename: Maxime
authors.initials: M
authors.lastname: Bergeron
authors.forename: Steven D
authors.initials: SD
authors.lastname: Hanes
authors.forename: François
authors.initials: F
authors.lastname: Robert
mesh_terms: D018844:Cyclin-Dependent Kinases / Q000502:physiology; D005656:Fungal Proteins / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D007535:Isomerases / Q000378:metabolism / Q000502:physiology*; D010443:Peptide Chain Termination, Translational; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism / Q000502:physiology*; D014176:Protein Biosynthesis; D012319:RNA Polymerase II / Q000737:chemistry / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D010770:Phosphotransferases; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases; D007535:Isomerases