6fuw

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Cryo-EM structure of the human CPSF160-WDR33-CPSF30 complex bound to the PAS AAUAAA motif at 3.1 Angstrom resolutionCryo-EM structure of the human CPSF160-WDR33-CPSF30 complex bound to the PAS AAUAAA motif at 3.1 Angstrom resolution

Structural highlights

6fuw is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CPSF1_HUMAN] Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. This subunit is involved in the RNA recognition step of the polyadenylation reaction.[1] [CPSF4_HUMAN] Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U).[2] [3] [WDR33_HUMAN] Essential for both cleavage and polyadenylation of pre-mRNA 3' ends.[4]

Publication Abstract from PubMed

Mammalian mRNA biogenesis requires specific recognition of a hexanucleotide AAUAAA motif in the polyadenylation signals (PAS) of precursor mRNA (pre-mRNA) transcripts by the cleavage and polyadenylation specificity factor (CPSF) complex. Here we present a 3.1-A-resolution cryo-EM structure of a core CPSF module bound to the PAS hexamer motif. The structure reveals the molecular interactions responsible for base-specific recognition, providing a rationale for mechanistic differences between mammalian and yeast 3' polyadenylation.

Structural basis of AAUAAA polyadenylation signal recognition by the human CPSF complex.,Clerici M, Faini M, Muckenfuss LM, Aebersold R, Jinek M Nat Struct Mol Biol. 2018 Jan 22. pii: 10.1038/s41594-017-0020-6. doi:, 10.1038/s41594-017-0020-6. PMID:29358758[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Kaufmann I, Martin G, Friedlein A, Langen H, Keller W. Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBO J. 2004 Feb 11;23(3):616-26. Epub 2004 Jan 29. PMID:14749727 doi:http://dx.doi.org/10.1038/sj.emboj.7600070
  2. ↑ Barabino SM, Hubner W, Jenny A, Minvielle-Sebastia L, Keller W. The 30-kD subunit of mammalian cleavage and polyadenylation specificity factor and its yeast homolog are RNA-binding zinc finger proteins. Genes Dev. 1997 Jul 1;11(13):1703-16. PMID:9224719
  3. ↑ Kaufmann I, Martin G, Friedlein A, Langen H, Keller W. Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBO J. 2004 Feb 11;23(3):616-26. Epub 2004 Jan 29. PMID:14749727 doi:http://dx.doi.org/10.1038/sj.emboj.7600070
  4. ↑ Shi Y, Di Giammartino DC, Taylor D, Sarkeshik A, Rice WJ, Yates JR 3rd, Frank J, Manley JL. Molecular architecture of the human pre-mRNA 3' processing complex. Mol Cell. 2009 Feb 13;33(3):365-76. doi: 10.1016/j.molcel.2008.12.028. PMID:19217410 doi:http://dx.doi.org/10.1016/j.molcel.2008.12.028
  5. ↑ Clerici M, Faini M, Muckenfuss LM, Aebersold R, Jinek M. Structural basis of AAUAAA polyadenylation signal recognition by the human CPSF complex. Nat Struct Mol Biol. 2018 Jan 22. pii: 10.1038/s41594-017-0020-6. doi:, 10.1038/s41594-017-0020-6. PMID:29358758 doi:http://dx.doi.org/10.1038/s41594-017-0020-6

6fuw, resolution 3.07Å

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