An interaction between U2AF 65 and CF I_m links the splicing and 3′ end processing machineries

The protein factor U2 snRNP Auxiliary Factor (U2AF) 65 is an essential component required for splicing and involved in the coupling of splicing and 3′ end processing of vertebrate pre-mRNAs. Here we have addressed the mechanisms by which U2AF 65 stimulates pre-mRNA 3′ end processing. We identify an arginine/serine-rich region of U2AF 65 that mediates an interaction with an RS-like alternating charge domain of the 59 kDa subunit of the human cleavage factor I (CF I_m), an essential 3′ processing factor that functions at an early step in the recognition of the 3′ end processing signal. Tethered functional analysis shows that the U2AF 65/CF I _m 59 interaction stimulates in vitro 3′ end cleavage and polyadenylation. These results therefore uncover a direct role of the U2AF 65/CF I_m 59 interaction in the functional coordination of splicing and 3′ end processing.