| Modification Notes |
Processing of the 3’ end of mRNA depends on several protein factors, one of which is the cleavage and polyadenylation specificity factor (CPSF). CPSF is required for both the cleavage of the mRNA precursor and for polyadenylation. CPSF, a multisubunit factor consisting of four subunits, is localized to the nucleoplasm and is excluded from cytoplasmic and nucleolar structures in HeLa cells. CPSF recognizes the AAUAAA signal in the pre-mRNA and interacts with other proteins to facilitate both RNA cleavage and poly(A) synthesis. The largest subunit of CPSF can, by itself, bind preferentially to AAUAAA-containing RNAs and binds specifically to both the suppressor of forked subunit of the cleavage stimulatory factor (CstF) and to poly (A) polymerase. U1 snRNP-A protein (U1A) interacts with and affects the activity of CPSF by stabilizing the interaction of CPSF with the AAUAAA-containing RNAs to increase the efficiency of polyadenylation. Efficient processing of 3’ core poly(A) site also requires sequences 76 nucleotides upstream of the AAUAA hexamer. The largest subunit is able to interact directly with the HIV-1 upstream element to direct a stable binding of CPSF to the pre-mRNA and enhance the efficiency of polyadenylation. |
