Figure 2. Cleavage and polyadenylation specificity factor subunit 6 (CPSF6) is a component of the mammalian cleavage factor I (CFIm) complex.

(A) CPSF6’s role in alternative polyadenylation. CPSF6, a component of the CFIm complex, is involved in the maturation of pre-mRNA into functional mRNA. CPSF6 controls alternative polyadenylation by selecting the polyadenylation signal. Cleavage and polyadenylation are controlled by upstream (UGUA, hexameric A[A/U]UAAA, and U-rich) and downstream (GU-rich and U-rich) cis-elements. UGUA is recognized by the CFIm complex (CPSF5₂ and either CPSF6₂ or CPSF7₂). CPSF5 binds directly to the UGUA element and anchors CPSF6 to the transcript. CPSF6 positions the complex at the appropriate cleavage and polyadenylation site and enhances RNA binding. CFIm complex interacts with the CFIIm complex, which is required for RNA cleavage [82]. The A[A/U]UAAA motif recruits the CPSF complex to promote cleavage stimulation factor (CstF). After cleavage the 3′ end of the transcript is then subjected to poly(A) tail addition by poly(A) polymerase. (B) Alternative polyadenylation. Human genes frequently encode more than one polyadenylation signal. The transcript isoforms that are derived from a single gene with two polyadenylation signals (PASs) are illustrated. When the gene uses the proximal PAS, the mature mRNA contains a short 3’UTR. By contrast, the use of a distal PAS results in an mRNA with a long 3’UTR. The ability of the CFIm complex to use the proximal polyadenylation signal instead of the distal signal is referred to as alternative polyadenylation. GOI, gene of interest.