Strange bedfellows: polyadenylation factors at the promoter.

Abstract

One of the more unexpected discoveries in the field of gene expression during the last few years has been the degree to which transcription of mRNA precursors is coupled to their subsequent processing into mature mRNAs. Much of this linkage involves the transcribing enzyme itself, RNA polymerase II (RNAP II), and specifically the repetitive C-terminal domain of its largest subunit (known simply as the CTD). A large body of evidence now indicates that the CTD has a significant role in enhancing the efficiency of all three of the major processing reactions—capping, splicing, and polyadenylation (for review, see Hirose and Manley 2000; Bentley 2002; Maniatis and Reed 2002; Proudfoot et al. 2002). This was initially surprising—all three reactions were known to occur just fine in vitro in the absence of transcription, or for that matter RNAP II and the CTD—but in retrospect it makes sense as a way to ensure accurate, efficient, and rapid processing of nascent pre-mRNAs. Precisely how the CTD functions is not entirely understood, especially in the more complex splicing and polyadenylation reactions, but a number of interactions with specific processing factors have been documented and these likely serve to help recruit the processing machinery to the pre-mRNA and then to stabilize or enhance the activity of these complexes. Interactions between the transcription and processing machineries extend beyond those by which RNAP II and the CTD stimulate processing (for review, see Manley 2002). For example, yeast capping enzymes seem able to repress transcription reinitiation, perhaps as a checkpoint to ensure that capping has been completed (Myers et al. 2002), whereas mammalian splicing factors can function in vitro to stimulate transcription initiation (Kwek et al. 2002) or elongation (Fong and Zhou 2001). In this brief review, we discuss evidence supporting the existence of a complex, evolutionarily conserved set of interactions that link even more tightly events that occur at the promoter to define the transcription start site and mRNA 5 end with those that occur at the other end of the gene to produce the mRNA 3 end and ultimately the transcription stop site.