title: TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA polymerase II.
abstract: Posttranslational modifications of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) specify a molecular recognition code that is deciphered by proteins involved in RNA biogenesis. The CTD is comprised of a repeating heptapeptide (Y(1)S(2)P(3)T(4)S(5)P(6)S(7)). Recently, phosphorylation of serine 7 was shown to be important for cotranscriptional processing of two snRNAs in mammalian cells. Here we report that Kin28/Cdk7, a subunit of the evolutionarily conserved TFIIH complex, is a Ser7 kinase. The ability of Kin28/Cdk7 to phosphorylate Ser7 is particularly surprising because this kinase functions at promoters of protein-coding genes, rather than being restricted to promoter-distal regions of snRNA genes. Kin28/Cdk7 is also known to phosphorylate Ser5 residues of the CTD at gene promoters. Taken together, our results implicate the TFIIH kinase in placing bivalent Ser5 and Ser7 marks early in gene transcription. These bivalent CTD marks, in concert with cues within nascent transcripts, specify the cotranscriptional engagement of the relevant RNA processing machinery.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Md Sohail
authors.initials: MS
authors.lastname: Akhtar
authors.forename: Martin
authors.initials: M
authors.lastname: Heidemann
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Tietjen
authors.forename: David W
authors.initials: DW
authors.lastname: Zhang
authors.forename: Rob D
authors.initials: RD
authors.lastname: Chapman
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
authors.forename: Aseem Z
authors.initials: AZ
authors.lastname: Ansari
mesh_terms: D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D018844:Cyclin-Dependent Kinases; C084210:Kin28 protein kinase, S cerevisiae; D012319:RNA Polymerase II