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. 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 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.

Structure

CPSF is a protein complex, consisting of four proteins: CPSF-73, CPSF-100, CPSF-30 and CPSF-160.

CPSF-73 is a zinc-dependent hydrolase which cleaves the mRNA precursor just downstream the polyadenylation signal sequence AAUAAA.[1]

CPSF-160 is the largest subunit of CPSF and directly binds to the AAUAAA polyadenylation signal.[2]

CPSF recruits 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 polynucleotide adenylyltransferase responsible for actually synthesizing the tail is a necessary prerequisite for cleavage, thus ensuring that cleavage and polyadenylation are tightly coupled processes.

Genes
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References
  1. Mandel, Corey R.; Kaneko, Syuzo; Zhang, Hailong; Gebauer, Damara; Vethantham, Vasupradha; Manley, James L.; Tong, Liang (26 November 2006). "Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease". Nature. 444 (7121): 953–956. doi:10.1038/nature05363. PMC 3866582. PMID 17128255.
  2. Murthy, Kanneganti G K; Manley, James L (1 November 1995). "The 160-kD subunit of human cleavage-polyadenylation specificity factor coordinates pre-mRNA 3'-end formation". Genes & Development. 9 (21): 2672–2683. doi:10.1101/gad.9.21.2672. PMID 7590244. Retrieved 17 December 2014.


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