CPSF

CPSF, or cleavage and polyadenylation specificity factor, is a conserved multi-subunit protein complex essential for the 3' end processing of most eukaryotic pre-mRNAs. It recognizes the polyadenylation signal AAUAAA and coordinates the cleavage of the transcript and the addition of the poly(A) tail, a step required for mRNA stability, export, and translation.

In vertebrates, the core CPSF complex comprises several subunits, including CPSF-160 (CPSF1), CPSF-100 (CPSF2), CPSF-73 (CPSF3), and CPSF-30 (CPSF4). It associates with RNA-binding factors such as WDR33 and Fip1 and with the scaffolding protein Symplekin. The complex interacts with other 3' end processing factors, notably CstF, to position the cleavage site downstream of the AAUAAA motif and recruit the poly(A) polymerase (PAP).

Mechanistically, WDR33 and CPSF-30 form the primary recognition module for the polyadenylation signal. CPSF-160 and CPSF-100 contribute to complex assembly and regulation, while CPSF-73 functions as the endonuclease that executes the cleavage event. Following cleavage, PAP is recruited and activated to synthesize the poly(A) tail, aided by Fip1 and other factors.

Dysregulation of CPSF-mediated processing can affect gene expression by altering mRNA stability and alternative polyadenylation, with implications for development and disease. The CPSF complex is evolutionarily conserved across eukaryotes, though subunit composition varies among organisms.

See also: CstF, CFIm, polyadenylation, pre-mRNA processing.