This work was supported by grants from the NIH-NIGMS to G.V. (GM64440) and S.B. (GM56663), from the German Research Foundation to A.M. (ME3135/1-1) and by the WCU project (305-20080089) from KMEST and grants from the National Research Foundation of Korea (NRF) (R31-2009-000-10032-0 and 2010-0011750) to M.K.
Nature Structural and Molecular Biology
Transcription factors, RNA polymerases, Phosphorylation, Genetic transcription -- Regulation, RNA-protein interactions
Phosphorylation of the C-terminal domain of RNA polymerase II controls the co-transcriptional assembly of RNA processing and transcription factors. Recruitment relies on conserved CTDinteracting domains that recognize different CTD phosphoisoforms during the transcription cycle, but the molecular basis for their specificity remains unclear. We show that the CTD-interacting domains of two transcription termination factors, Rtt103 and Pcf11, achieve high affinity and specificity both by specifically recognizing the phosphorylated CTD and by cooperatively binding to neighboring CTD repeats. Single amino acid mutations at the protein-protein interface abolish cooperativity and affect recruitment at the 3′-end processing site in vivo. We suggest that this cooperativity provides a signal-response mechanism to ensure that its action is confined only to proper polyadenylation sites where Serine 2 phosphorylation density is highest.
Lunde, B. M., Reichow, S. L., Kim, M., Suh, H., Leeper, T. C., Yang, F., ... & Varani, G. (2010). Cooperative interaction of transcription termination factors with the RNA polymerase II C-terminal domain. Nature structural & molecular biology, 17(10), 1195.