Role of Ser7 phosphorylation of the CTD during transcription of snRNA genes.

The largest subunit of RNA polymerase (pol) II, Rpb1, contains an unusual carboxyl-terminal domain (CTD) composed of consecutive repeats of the sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser (Y 1S 2P 3T 4S 5P 6S 7). During transcription, Ser2, Ser5 and Ser7 are subjected to dynamic phosphorylation and dephosphorylation by CTD kinases and phosphatases, creating a characteristic CTD phosphorylation pattern along genes. This CTD "code" allows the coupling of transcription with co-transcriptional RNA processing, through the timely recruitment of the appropriate factors at the right point of the transcription cycle. In mammals, phosphorylation of Ser7 (Ser7P) is detected on all pol II-transcribed genes, but is only essential for expression of a sub-class of genes encoding small nuclear (sn)RNAs. The molecular mechanisms by which Ser7P influences expression of these particular genes are becoming clearer. Here, I discuss our recent findings clarifying how Ser7P facilitates transcription of these genes and 3'end processing of the transcripts, through recruitment of the RPAP2 phosphatase and the snRNA gene-specific Integrator complex.