RNA polymerase II conducts a symphony of pre-mRNA processing activities

Abstract

RNA polymerase II (RNAP II) and its associated factors interact with a diverse collection of nuclear proteins during the course of precursor messenger RNA synthesis. This growing list of known contacts provides compelling evidence for the existence of large multifunctional complexes, a.k.a. transcriptosomes, within which the biosynthesis of mature mRNAs is coordinated. Recent studies have demonstrated that the unique carboxy-terminal domain (CTD) of the largest subunit of RNAP II plays an important role in recruiting many of these activities to the transcriptional machinery. Throughout the transcription cycle the CTD undergoes a variety of covalent and structural modifications which can, in turn, modulate the interactions and functions of processing factors during transcription initiation, elongation and termination. New evidence suggests that the possibility that interaction of some of these processing factors with the polymerase can affect its elongation rate. Besides the CTD, proteins involved in pre-mRNA processing can interact with general transcription factors (GTFs) and transcriptional activators, which associate with polymerase at promoters. This suggests a mechanism for the recruitment of specific processing activities to different transcription units. This harmonic integration of transcriptional and post-transcriptional activities, many of which once were considered to be functionally isolated within the cell, supports a general model for the coordination of gene expression by RNAP II within the nucleus.