@article{2da7570b1f43483194cce48c025797f7,
title = "HnRNP A1 Proofreads 3' Splice Site Recognition by U2AF",
abstract = "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 invitro and invivo depletion, as well as reconstitution assays using purified components, to identify hnRNP A1 as an RNA binding protein that allows U2AF todiscriminate 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.",
author = "Tavanez, {Joao Paulo} and Tobias Madl and Hamed Kooshapur and Michael Sattler and Juan Valc{\'a}rcel",
note = "Funding Information: We thank numerous colleagues in our institutes who have provided valuable input throughout this project and useful comments on the manuscript, particularly P. Papasaikas for bioinformatic predictions, A. Corrionero and R. Tejedor for help with figures preparation, and the CRG Proteomics Facility for mass-spectrometry determination. J.P.T. was supported by an EMBO postdoctoral fellowship. T.M. thanks the Austrian Science Fund (FWF) and EMBO for postdoctoral fellowships. H.K. acknowledges support by the TUM Graduate School. Work in J.V.'s laboratory is supported by Fundaci{\'o}n Marcelino Bot{\'i}n, Fundaci{\'o}n Alicia Koplowicz, AICR, Consolider RNAREG, EURASNET, Ministerio de Ciencia e Innovaci{\'o}n, and AGAUR. Work in M.S.'s laboratory is supported by the European Commission, grant NIM3 number 226507, and the Deutsche Forschungsgemeinschaft. ",
year = "2012",
month = feb,
day = "10",
doi = "10.1016/j.molcel.2011.11.033",
language = "English",
volume = "45",
pages = "314--329",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",
}