Cleavage and polyadenylation specificity factor

"CPSF" redirects here. For Comité Paralympique et Sportif Français, see French Paralympic and Sports Committee.

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.[1]

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."[2] It is required to induce RNA polymerase pausing once it recognizes a functional PAS.[3] 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.[2][4] 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.[4][5]

  1. ^ Mandel CR, Bai Y, Tong L (April 2008). "Protein factors in pre-mRNA 3'-end processing". Cellular and Molecular Life Sciences. 65 (7–8): 1099–1122. doi:10.1007/s00018-007-7474-3. PMC 2742908. PMID 18158581.
  2. ^ a b Schönemann L, Kühn U, Martin G, Schäfer P, Gruber AR, Keller W, et al. (November 2014). "Reconstitution of CPSF active in polyadenylation: recognition of the polyadenylation signal by WDR33". Genes & Development. 28 (21): 2381–2393. doi:10.1101/gad.250985.114. PMC 4215183. PMID 25301781.
  3. ^ Cite error: The named reference Murphy_2021 was invoked but never defined (see the help page).
  4. ^ a b Shi Y, Manley JL (May 2015). "The end of the message: multiple protein-RNA interactions define the mRNA polyadenylation site". Genes & Development. 29 (9): 889–897. doi:10.1101/gad.261974.115. PMC 4421977. PMID 25934501.
  5. ^ Sun Y, Zhang Y, Hamilton K, Manley JL, Shi Y, Walz T, Tong L (February 2018). "Molecular basis for the recognition of the human AAUAAA polyadenylation signal". Proceedings of the National Academy of Sciences of the United States of America. 115 (7): E1419–E1428. Bibcode:2018PNAS..115E1419S. doi:10.1073/pnas.1718723115. PMC 5816196. PMID 29208711.