| Structural highlights
6i1d is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | YSH1, BRR5, YLR277C (Baker's yeast), MPE1, YKL059C, YKL316 (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[YSH1_YEAST] Component of the cleavage and polyadenylation factor (CPF) complex, which plays a key role in polyadenylation-dependent pre-mRNA 3'-end formation and cooperates with cleavage factors including the CFIA complex and NAB4/CFIB. Has endonuclease activity.[1] [MPE1_YEAST] Component of the cleavage and polyadenylation factor (CPF) complex, which plays a key role in polyadenylation-dependent pre-mRNA 3'-end formation and cooperates with cleavage factors including the CFIA complex and NAB4/CFIB.
Publication Abstract from PubMed
Cleavage and polyadenylation factor (CPF/CPSF) is a multi-protein complex essential for formation of eukaryotic mRNA 3' ends. CPF cleaves pre-mRNAs at a specific site and adds a poly(A) tail. The cleavage reaction defines the 3' end of the mature mRNA, and thus the activity of the endonuclease is highly regulated. Here, we show that reconstitution of specific pre-mRNA cleavage with recombinant yeast proteins requires incorporation of the Ysh1 endonuclease into an eight-subunit "CPFcore" complex. Cleavage also requires the accessory cleavage factors IA and IB, which bind substrate pre-mRNAs and CPF, likely facilitating assembly of an active complex. Using X-ray crystallography, electron microscopy, and mass spectrometry, we determine the structure of Ysh1 bound to Mpe1 and the arrangement of subunits within CPFcore. Together, our data suggest that the active mRNA 3' end processing machinery is a dynamic assembly that is licensed to cleave only when all protein factors come together at the polyadenylation site.
Activation of the Endonuclease that Defines mRNA 3' Ends Requires Incorporation into an 8-Subunit Core Cleavage and Polyadenylation Factor Complex.,Hill CH, Boreikaite V, Kumar A, Casanal A, Kubik P, Degliesposti G, Maslen S, Mariani A, von Loeffelholz O, Girbig M, Skehel M, Passmore LA Mol Cell. 2019 Jan 31. pii: S1097-2765(18)31099-2. doi:, 10.1016/j.molcel.2018.12.023. PMID:30737185[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ryan K, Calvo O, Manley JL. Evidence that polyadenylation factor CPSF-73 is the mRNA 3' processing endonuclease. RNA. 2004 Apr;10(4):565-73. PMID:15037765
- ↑ Hill CH, Boreikaite V, Kumar A, Casanal A, Kubik P, Degliesposti G, Maslen S, Mariani A, von Loeffelholz O, Girbig M, Skehel M, Passmore LA. Activation of the Endonuclease that Defines mRNA 3' Ends Requires Incorporation into an 8-Subunit Core Cleavage and Polyadenylation Factor Complex. Mol Cell. 2019 Jan 31. pii: S1097-2765(18)31099-2. doi:, 10.1016/j.molcel.2018.12.023. PMID:30737185 doi:http://dx.doi.org/10.1016/j.molcel.2018.12.023
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