Abstract
Pre-mRNA3’-end processing is an essential post-transcriptional step. It is composed of two reactions: cleavage at the pre-mRNA 3’ end that allows release of mRNA from the transcription site and addition of the poly(A) tail that controls nuclear export, stability and the translation of the mature transcript. Several studies show that 3’-end processing is globally inhibited during DNA damage and that deregulation of this process may contribute to tumor development. Our work focused on 3’-end processing regulation of (i) p53 pre-mRNA during DNA damage (ii) MSH6 pre-mRNA involved in Lynch syndrome. (i) We have shown that p53 pre-mRNA resists to DNA damagedependent inhibition of 3’-end processing through the recruitment of the protein factor hnRNP H/F on a RNA structure called G-quadruplex located downstream of the cleavage site. (ii) We then identified a duplication of 20 nucleotides upstream of the polyadenylation signal at the MSH6 pre-mRNA in two distinct families with Lynch syndrome. This duplication causes a reduction of MSH6 pre-mRNA 3’-end processing efficiency and in consequence, it may be causal of Lynch syndrome.