CPSF73 Protein, Human

CPSF73 is a component of the cleavage and polyadenylation specificity factor (CPSF) complex, playing a pivotal role in pre-mRNA 3'-end formation by recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to facilitate cleavage and poly(A) addition. It exhibits endonuclease activity, functioning as an mRNA 3'-end-processing endonuclease and participating in histone 3'-end pre-mRNA processing. As a U7 snRNP-dependent protein, CPSF73 mediates both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a processive 5' to 3' exonuclease to degrade the downstream cleavage product (DCP). Cleavage occurs after the 5'-ACCCA-3' sequence in histone pre-mRNA, leaving a 3' hydroxyl group on the upstream fragment containing the stem-loop (SL) and a 5' phosphate on the DCP starting with CU nucleotides. Its U7-dependent exonuclease activity persists even after complete removal of the U7-binding site. CPSF73 binds to the DCP of histone pre-mRNAs and cleaved DCP RNA substrate in a U7 snRNP-dependent manner and is essential for S-phase entry/progression in the cell cycle. Additionally, through interaction with ISY1 (By similarity), it contributes to selective miRNA processing during embryonic stem cell differentiation and is required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a (By similarity). For the pri-miR-290-295 and pri-miR-96-183 primary transcripts, CPSF73 is specifically involved in the biogenesis of miR-290 and miR-96, respectively (By similarity).