THE ROLE OF MULTISITE PHOSPHORYLATION IN THE REGULATION OF RNA-POLYMERASE-II ACTIVITY

This chapter discusses (a) the relationship between the state of carboxy-terminal domain (CTD) phosphorylation and the progression of RNAP II through the transcription cycle; (b) the enzymes involved in modulating the state of CTD phosphorylation; and (c) the potential consequences of modifications that occur within the CTD. RNA polymerase (RNAP) II is structurally distinct from both RNAP I that transcribes heavy ribosomal RNA (rRNA) and RNAP III that transcribes a variety of small RNAs, including 5-S rRNA and transfer RNA (tRNA). RNAP II transcribes the greatest diversity of genes, and hence must be able to assemble into preinitiation complexes on a variety of different promoters. The largest subunit of RNAP I1 contains at its c-terminus an unusual domain, consisting of multiple heptapeptide repeats of the consensus sequence, Tyr-Ser-Pro-Thr-Ser-Pro-Ser. This c-terminal domain (CTD) is conserved in evolution and is essential for cell viability. The functions for the CTD is regulated by reversible phosphorylation that include: (a) mediating the interaction of RNAP II, with the preinitiation complex; (b) mediating the release of RNAP I1 from the initiated complex; (c) facilitating the progression of RNAP II through nucleosomes (X); (d) affecting cotranscriptional splicing, by facilitating the association of splicing factors, with the elongation complex; and (e) influencing the specificity of pausing and termination. © 1994, Academic Press Inc.