Reciprocal Links between Pre-messenger RNA 3′-End Processing and Genome Stability

The 3′-end processing of most pre-messenger RNAs (pre-mRNAs) involves RNA cleavage and polyadenylation and is coupled to transcription termination. In both yeast and human cells, pre-mRNA 3′-end cleavage is globally inhibited by DNA damage. Recently, further links between pre-mRNA 3′-end processing and the control of genome stability have been uncovered, as reviewed here. Upon DNA damage, various genes related to the DNA damage response (DDR) escape 3′-end processing inhibition or are regulated through alternative polyadenylation (APA). Conversely, various pre-mRNA 3′-end processing factors prevent genome instability and are found at sites of DNA damage. Finally, the reciprocal link between pre-mRNA 3′-end processing and genome stability control seems important because it is conserved in evolution and involved in disease development.