Cleavage and polyadenylation specificity factor

Cleavage and polyadenylation specificity factor (CPSF) 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. In eukaryotes, messenger RNA precursors (pre-mRNA) are transcribed in the nucleus from DNA by the enzyme, RNA polymerase II. The pre-mRNA must undergo post-transcriptional modifications, forming mature RNA (mRNA), before they can be transported into the cytoplasm for translation into proteins. The post-transcriptional modifications are: the addition of a 5' m7G cap, splicing of intronic sequences, and 3' cleavage and polyadenylation.

According to Schönemann et al., "CPSF recognizes the polyadenylation signal (PAS), providing sequence specificity in pre-mRNA cleavage and polyadenylation, and catalyzes pre-mRNA cleavage." It is required to induce RNA polymerase pausing once it recognizes a functional PAS. It is the first protein to bind to the signaling region near the cleavage site of the pre-mRNA, to which the poly(A) tail will be added by polynucleotide adenylyltransferase. The 10-30 nucleotide upstream signaling region of the cleavage site, polyadenylation signal (PAS), has the canonical nucleotide sequence AAUAAA, which is highly conserved across the vast majority of pre-mRNAs. The AAUAAA region is usually defined by a cytosine/adenine (CA) dinucleotide, which is the preferred sequence, that is 5' to the site of the endonucleolytic cleavage. A second downstream signaling region, located approximately 40 nucleotides downstream from the cleavage site on the portion of the pre-mRNA that is cleaved before polyadenylation, consists of a U/GU-rich region required for efficient processing. This downstream fragment is degraded. The mature RNA are transported into the cytoplasm, where they are translated into proteins.