Cleavage and polyadenylation specificity factor (CPSF) (or Cleavage polyadenylation stimulating factor) is involved in the cleavage of the 3' signaling region from a newly synthesized pre-messenger RNA (pre-mRNA) molecule in the process of gene transcription. It is the first protein to bind to the signaling region near the cleavage site of the pre-mRNA, to which the polyadenine tail will be added by polyadenylate polymerase. The upstream signaling region has the canonical nucleotide sequence AAUAAA, which is highly conserved across the vast majority of pre-mRNAs. A second downstream signaling region, located on the portion of the pre-mRNA that is cleaved before polyadenylation, consists of a GU-rich region required for efficient processing.
CPSF is a protein complex consisting of four proteins: CPSF-73, CPSF-100, CPSF-30 and CPSF-160. CPSF-73 is believed to be the endonuclease which cleaves mRNA precursor and the crystal structure of its N-terminal domain has been resolved. CPSF recruits additional proteins to the 3' region. Identified proteins that are coordinated by CPSF activity include: cleavage stimulatory factor and the two poorly understood cleavage factors. The binding of the polyadenine polymerase responsible for actually synthesizing the tail is a necessary prerequisite for cleavage, thus ensuring that cleavage and polyadenylation are tightly coupled processes.