The primary components of the RNA biogenesis machinery and their interactions with the RNA polymerase II C-terminal domain (CTD). Briefly, hypophosphorylated Pol II assembles at the preinitiation complex (PIC) with the Mediator and general transcription factors (GTFs), with TFIIH associating last. The TFIIH-associated kinase Kin28 phosphorylates Ser5 (shown in red) and Ser7 (shown in purple) on the CTD. Mediator-associated kinase Srb10 also contributes to the phosphorylation of Ser5-P. This mark enables promoter release and mediates interactions with the capping enzyme (CE) complex, Nrd1 component of termination machinery, and Set1 histone methyltransferase, which places trimethyl marks on histone H3K4. The Ser5-P mark also facilitates recruitment of Bur1 kinase. Bur1 places initial Ser2-P marks, which facilitate recruitment of Ctk1 kinase, and continues to replenish Ser7-P marks during elongation. Ctk1 is the primary Ser2 kinase, and its phosphorylation recruits splicing machinery (SP) through Prp40, as well as Set2 histone methyltransferase, which places di- and trimethyl marks on histone H3K36. Cleavage and polyadenylation (PA) machinery are recruited through many factors associating with the CTD. One of the factors, Pcf11, binds cooperatively to Ser2-P with Rtt103. The exonuclease complex (Exo) is also recruited through interaction between CTD and Rtt103 and through cooperative interaction between Rtt103 and Pcf11. Finally, the hypophosphorylated CTD is regenerated through three CTD phosphatases. Ser2-P is removed by the phosphatase Fcp1, while two phosphatases, Rtr1 and Ssu72, combine to remove Ser5-P marks during elongation and at termination, respectively. Upon de-phosphorylation, Pol II is released with the assistance of a mechanism involving Pcf11 and can begin another cycle of transcription.
