7zgp
Polymerase module of CPF in complex with Mpe1 and a pre-cleaved CYC1 RNA
Structural highlights
FunctionCFT1_YEAST RNA-binding 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. Involved in poly(A) site recognition. May be involved in coupling transcription termination and mRNA 3'-end formation.[1] [2] Publication Abstract from PubMedMost eukaryotic messenger RNAs (mRNAs) are processed at their 3' end by the cleavage and polyadenylation specificity factor (CPF/CPSF). CPF mediates the endonucleolytic cleavage of the pre-mRNA and addition of a polyadenosine (poly(A)) tail, which together define the 3' end of the mature transcript. The activation of CPF is highly regulated to maintain the fidelity of RNA processing. Here, using cryo-EM of yeast CPF, we show that the Mpe1 subunit directly contacts the polyadenylation signal sequence in nascent pre-mRNA. The region of Mpe1 that contacts RNA also promotes the activation of CPF endonuclease activity and controls polyadenylation. The Cft2 subunit of CPF antagonizes the RNA-stabilized configuration of Mpe1. In vivo, the depletion or mutation of Mpe1 leads to widespread defects in transcription termination by RNA polymerase II, resulting in transcription interference on neighboring genes. Together, our data suggest that Mpe1 plays a major role in accurate 3' end processing, activating CPF, and ensuring timely transcription termination. Mpe1 senses the binding of pre-mRNA and controls 3' end processing by CPF.,Rodriguez-Molina JB, O'Reilly FJ, Fagarasan H, Sheekey E, Maslen S, Skehel JM, Rappsilber J, Passmore LA Mol Cell. 2022 Jul 7;82(13):2490-2504.e12. doi: 10.1016/j.molcel.2022.04.021. , Epub 2022 May 17. PMID:35584695[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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