Structural Insights into the Human Pre-mRNA 3'-End Processing Machinery.

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Tytuł:: Structural Insights into the Human Pre-mRNA 3'-End Processing Machinery.
Autorzy:: Zhang Y; Laboratory of Molecular Electron Microscopy, Rockefeller University, New York, NY 10065, USA.
Sun Y; Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Shi Y; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Walz T; Laboratory of Molecular Electron Microscopy, Rockefeller University, New York, NY 10065, USA. Electronic address: .
Tong L; Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: .
Źródło:: Molecular cell [Mol Cell] 2020 Feb 20; Vol. 77 (4), pp. 800-809.e6. Date of Electronic Publication: 2019 Dec 03.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Cambridge Ma : Cell Press
Original Publication: Cambridge, Mass. : Cell Press, c1997-
MeSH Terms:: Cleavage And Polyadenylation Specificity Factor/*chemistry
Cleavage And Polyadenylation Specificity Factor/genetics ; Cleavage Stimulation Factor/chemistry ; Cryoelectron Microscopy ; Humans ; Models, Molecular ; Mutation ; RNA 3' End Processing ; RNA Precursors/metabolism ; RNA, Messenger/metabolism
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Grant Information:: R01 GM090056 United States GM NIGMS NIH HHS; P41 GM103310 United States GM NIGMS NIH HHS; P41 RR001209 United States RR NCRR NIH HHS; R35 GM149294 United States GM NIGMS NIH HHS; S10 OD019994 United States OD NIH HHS; R35 GM118093 United States GM NIGMS NIH HHS
Contributed Indexing:: Keywords: CPSF160; CPSF73; alternative polyadenyltation; cleavage and polyadenylation; polyadenylation signal
Substance Nomenclature:: 0 (CPSF2 protein, human)
0 (Cleavage And Polyadenylation Specificity Factor)
0 (Cleavage Stimulation Factor)
0 (RNA Precursors)
0 (RNA, Messenger)
Entry Date(s):: Date Created: 20191208 Date Completed: 20200914 Latest Revision: 20231231
Update Code:: 20231231
PubMed Central ID:: PMC7036032
DOI:: 10.1016/j.molcel.2019.11.005
PMID:: 31810758
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The mammalian pre-mRNA 3'-end-processing machinery consists of cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), and other proteins, but the overall architecture of this machinery remains unclear. CPSF contains two functionally distinct modules: a cleavage factor (mCF) and a polyadenylation specificity factor (mPSF). Here, we have produced recombinant human CPSF and CstF and examined these factors by electron microscopy (EM). We find that mPSF is the organizational core of the machinery, while the conformations of mCF and CstF and the position of mCF relative to mPSF are highly variable. We have identified by cryo-EM a segment in CPSF100 that tethers mCF to mPSF, and we have named it the PSF interaction motif (PIM). Mutations in the PIM can abolish CPSF formation, indicating that it is a crucial contact in CPSF. We have also obtained reconstructions of mCF and CstF77 by cryo-EM, assembled around the mPSF core.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Copyright © 2019 Elsevier Inc. All rights reserved.)

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