Paper ID: 345
University of Oxford, Biochemistry Department, Oxford (United Kingdom)
Reversible phosphorylation of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is important for coordinated regulation of transcription and maturation of functional mRNA, yet the molecular mechanism underpinning CTD function remains unclear.
CTD consists of multiple repeats of the consensus sequence (Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7) where it can be phosphorylated on Y1, S2, T4, S5, and S7P. While regulation and function of S2P have been extensively studied, role of T4P as well as kinases and phosphatases responsible for regulation of this recently identified modification are not known. We observe that S2P, T4P and Y1P co-occur on CTD at the end of the transcription cycle in fission yeast suggesting that these marks might be important at this stage. We show that conserved PP1 phosphatase is involved in T4P regulation and lack of its activity leads to genome –wide transcription termination defect. Our findings reinforce the importance of CTD phosphorylation in regulation of Pol II transcription and provide mechanistic insights into CTD function.