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Dynamics in Fip1 regulate eukaryotic mRNA 3' end processing.

Authors :
Kumar A
Yu CWH
Rodríguez-Molina JB
Li XH
Freund SMV
Passmore LA
Source :
Genes & development [Genes Dev] 2021 Nov 01; Vol. 35 (21-22), pp. 1510-1526. Date of Electronic Publication: 2021 Sep 30.
Publication Year :
2021

Abstract

Cleavage and polyadenylation factor (CPF/CPSF) is a multiprotein complex essential for mRNA 3' end processing in eukaryotes. It contains an endonuclease that cleaves pre-mRNAs, and a polymerase that adds a poly(A) tail onto the cleaved 3' end. Several CPF subunits, including Fip1, contain intrinsically disordered regions (IDRs). IDRs within multiprotein complexes can be flexible, or can become ordered upon interaction with binding partners. Here, we show that yeast Fip1 anchors the poly(A) polymerase Pap1 onto CPF via an interaction with zinc finger 4 of another CPF subunit, Yth1. We also reconstitute a fully recombinant 850-kDa CPF. By incorporating selectively labeled Fip1 into recombinant CPF, we could study the dynamics of Fip1 within the megadalton complex using nuclear magnetic resonance (NMR) spectroscopy. This reveals that a Fip1 IDR that connects the Yth1- and Pap1-binding sites remains highly dynamic within CPF. Together, our data suggest that Fip1 dynamics within the 3' end processing machinery are required to coordinate cleavage and polyadenylation.<br /> (© 2021 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.)

Details

Language :
English
ISSN :
1549-5477
Volume :
35
Issue :
21-22
Database :
MEDLINE
Journal :
Genes & development
Publication Type :
Academic Journal
Accession number :
34593603
Full Text :
https://doi.org/10.1101/gad.348671.121