5 Phosphorylation of RNA Polymerase II as a Transcriptional Regulatory Mechanism

Abstract

OVERVIEW
The largest subunit of RNA polymerase II (RNA pol II) contains at its carboxyl terminus an unusual domain consisting of tandem repeats of the consensus sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. The extensive phosphorylation of this domain is thought to play an important role in the initiation phase of transcription and may be of regulatory significance. The results from a variety of studies suggest that each round of transcription is associated with the reversible phosphorylation of the carboxy-terminal domain (CTD). The transcription cycle of RNA pol II is thought to involve (1) the interaction of the unphosphorylated form of RNA polymerase with the promoter to which specific transcription factors have previously bound, (2) the extensive phosphorylation of the CTD by a template-associated kinase either prior to or concomitant with the initiation of the transcript, (3) disruption of the initiation complex and elongation of the transcript by the phosphorylated enzyme, and (4) release from the template and dephosphorylation. The potential significance of this phosphorylation with respect both to our understanding of the basic mechanisms of transcription and to the regulation of RNA pol II activity in general is discussed. In this paper, we also review our present understanding of the protein kinases that may be responsible for the phosphorylation of RNA pol II.

INTRODUCTION
RNA pol II is a multisubunit enzyme composed of two large subunits, with molecular weights in excess of 100,000, and a complex array of small subunits (for review, see Sawadogo and Sentenac 1990; Woychik and Young 1990). The largest subunit...