mRNA represents an important intermediate in protein synthesis. Cleavage and polyadenylation at the 3’end is carried out by complex machinery that is positioned through interactions with the mRNA transcript. When more than one potential poly(A) exists for a single gene this provides the opportunity for multiple mRNA isoforms to occur that may differ in their coding region or simply the length of their 3’UTR. This is referred to as alternative polyadenylation (APA) and has been linked to embryonic development, cell proliferation and multiple human diseases including cancer. The method by which alternative polyadenylation sites are chosen remains a relative mystery.
Temperature sensitive knockout of 3’end processing complex subunits generally induced a switch to longer mRNA transcripts in Saccharomyces cerevisiae. A similar lengthening was seen after treating cells with the adenosine anologue cordycepin. Furthermore genes that are able to undergo alternative polyadenylation tend to have a wider nucleosome-free region at their 3’end indicating that the ability to undergo APA is determined in part by the intrinsic higher ordering of the gene itself.