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Abstract
3’ processing of mRNA precursors is frequently coupled to transcription by RNA polymerase II (RNAP II). This coupling is well known to involve the C-terminal domain of the RNAP II largest subunit, but a variety of other transcription-associated factors have also been suggested to mediate coupling. Our recent studies have provided direct evidence that transcriptional activators can enhance the efficiency of transcription-coupled 3’ processing. In this point-of-view, we discuss the mechanisms that underlie coupling, and their implications for control of alternative polyadenylation, which is emerging as a significant regulator of cell growth control.
Acknowledgments
Work from the authors' lab is supported by grants from the NIH (J.L.M.).
Figures and Tables
Figure 1 Transcriptional activation and poly(A) site use. In many mRNAs containing multiple poly(A) sites, promoter-proximal sites are weaker than distal ones. Weakly transcribed genes, or genes on which transcription and 3′ processing are poorly coupled, will tend to polyadenylate less efficiently, leading to preferential use of distal poly(A) sites. This will result in long 3′ UTRs containing repressive sites, thus lowering protein expression. In contrast, strong transcriptional activation and the resulting enhanced 3′ processing efficiency will lead to use of proximal poly(A) sites, shorter 3′ UTRS and increased protein expression.
