Revised “phospho-CTD cycle.” (a) (I) For protein-coding genes, RNAPII is recruited to the promoter with an unphosphorylated CTD (IIA form); moreover, it appears that CTD phosphorylation prior to preinitiation complex (PIC) formation has an inhibitory effect on transcription. (II) Upon preinitiation complex formation, the CTD is phosphorylated at the Ser5 (black) and Ser7 (red) positions. (III) During elongation, an increase in Ser2 phosphorylation (green) produces the hyperphosphorylated form of the CTD, which is probably an ensemble of singly, doubly, and triply phosphorylated heptads. (IV) As the polymerase elongates towards the 3′ end of the gene, the activity of Ser5-specific phosphatases decreases the Ser5 phosphorylation levels, while the Ser2 and Ser7 phosphate levels remain largely unchanged. (b) (I) For noncoding genes, RNAPII is also recruited to the promoter with an unphosphorylated CTD (IIA form), and CTD phosphorylation prior to preinitiation complex (PIC) formation seems to inhibit transcription. (II) Upon preinitiation complex formation, the CTD phosphorylation of Ser5 (black) and Ser7 (red) increases. (III) During elongation, Ser2 phosphorylation (green) increases, while Ser7 phosphorylation begins to decline, presumably due to the activity of a yet unidentified Ser7 phosphatase. (IV) At the 3′ end of the gene, the activity of Ser5-specific phosphatases decreases the Ser5 phosphorylation levels, Ser7 phosphorylation levels continue to decrease, and Ser2 phosphate levels remain largely unchanged.
