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Tavanez, J.P.* ; Madl, T. ; Kooshapur, H. ; Sattler, M. ; Valcárcel, J.*

hnRNP A1 proofreads 3' splice site recognition by U2AF.

Mol. Cell 45, 314-329 (2012)
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One of the earliest steps in metazoan pre-mRNA splicing involves binding of U2 snRNP auxiliary factor (U2AF) 65 KDa subunit to the polypyrimidine (Py) tract and of the 35 KDa subunit to the invariant AG dinucleotide at the intron 3' end. Here we use in vitro and in vivo depletion, as well as reconstitution assays using purified components, to identify hnRNP A1 as an RNA binding protein that allows U2AF to discriminate between pyrimidine-rich RNA sequences followed or not by a 3' splice site AG. Biochemical and NMR data indicate that hnRNP A1 forms a ternary complex with the U2AF heterodimer on AG-containing/uridine-rich RNAs, while it displaces U2AF from non-AG-containing/uridine-rich RNAs, an activity that requires the glycine-rich domain of hnRNP A1. Consistent with the functional relevance of this activity for splicing, proofreading assays reveal a role for hnRNP A1 in U2AF-mediated recruitment of U2 snRNP to the pre-mRNA.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Pre-messeneger-RNA; Ribonucleoprotein auxiliary factor; Spinal muscular-atrophy; Branch site; Binding-Proteins; Polypyrimidine tracts; Annealing Activity; Telomeric repeats; Structural Basis; Sex-lethal
Language
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Journal Molecular Cell
Quellenangaben Volume: 45, Issue: 3, Pages: 314-329 Article Number: , Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503000-001
PubMed ID 22325350
DOI 10.1016/j.molcel.2011.11.033
WOS ID WOS:000300481100007
Scopus ID 84856786440
Erfassungsdatum 2012-03-27
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