Chunk #27 — REGULATORY ELEMENTS IN THE UNTRANSLATED REGIONS — Genetic variants at the 3′UTR — 3′UTR length and alteration of the polyadenylation signal
One important mechanism causing alteration in the 3′UTR length is the modification of the polyadenylation signal. Like the 5′ cap on mature mRNA, the stability, nuclear export and translation is also regulated by a stretch of adenine nucleotides that are added at the 3′end of the mRNA by specialized enzymes. The cleavage and polyadenylation specificity factor (CPSF) recognizes the specific sequence AAUAAA on the pre-mRNA and cuts 3′UTR about 10–30 nucleotides downstream of its binding site. Other proteins, such as the cleavage stimulation factor (CstF) and cleavage factors (CFI, CFII) work in concert creating, together with CPSF, the RNA-cleavage complex. Once the RNA is cut, the polyadenylate polymerase adds adenosine monophosphates creating the poly-A tail.47
