Deciphering the RNA polymerase II CTD code in fission yeast.

The RNA polymerase II carboxy-terminal domain (CTD) consists of tandem Y(1)S(2)P(3)T(4)S(5)P(6)S(7) repeats. Dynamic remodeling of the CTD, especially its serine phosphorylation pattern, conveys informational cues about the transcription apparatus to a large ensemble of CTD-binding proteins. Our genetic dissection of fission yeast CTD function provides insights to the "CTD code." Two concepts stand out. First, the Ser2 requirement for transcription during sexual differentiation is bypassed by subtracting Ser7, signifying that imbalance in the phosphorylation array, not absence of a phospho-CTD cue, underlies a CTD-associated pathology. Second, the essentiality of Ser5 for vegetative growth is circumvented by covalently tethering mRNA capping enzymes to the CTD, thus proving that capping enzyme recruitment is a chief function of the Ser5-PO(4) mark. This illustrates that a key "letter" in the CTD code can be neutralized by delivering its essential cognate receptor to the transcription complex via an alternative route.