A compendium of RNA-binding motifs for decoding gene regulation

• Type of Material: Article
• Authors: Debashish Ray, University of Toronto; Hilal Kazan, University of Toronto; Kate B. Cook, University of Toronto; Matthew T. Weirauch, University of Toronto; Hamed S. Najafabadi, University of Toronto; Xiao Li, University of Toronto; Serge Gueroussov, University of Toronto; Mihai Albu, University of Toronto; Hong Zheng, University of Toronto; Ally Yang, University of Toronto; Hong Na, University of Toronto; Manuel Irimia, University of Toronto; Leah H. Matzat, National Institutes of Health; Ryan K. Dale, National Institutes of Health; Sarah A. Smith, University of Pennsylvania; Christopher A. Yarosh, University of Pennsylvania; Seth Kelly, Emory University; Behnam Nabet, University of Pennsylvania; Desirea Mecenas, New York University; Weimin Li, University of Wisconsin; Rakesh S. Laishram, University of Wisconsin; Mei Qiao, Children’s Cancer Research Institute; Howard D. Lipshitz, University of Toronto; Fabio Piano, New York University; Anita Corbett, Emory University; Russ P. Carstens, University of Pennsylvania; Brendan J. Frey, University of Toronto; Richard A. Anderson, University of Wisconsin; Kristen W. Lynch, University of Pennsylvania; Luiz O. F. Penalva, Children’s Cancer Research Institute
• Language: English
• Date: 2013-07-11
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Macmillan Publishers Limited. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/nature12311
• Title of Journal or Parent Work: Nature
• ISSN: 0028-0836
• Volume: 499
• Issue: 7457
• Start Page: 172
• End Page: 177
• Grant/Funding Information: H.S.N. holds a Charles H. Best Fellowship and was funded partially by awards from CIFAR to T.R.H. and B.J.F. M.I. is the recipient of an HFSP LT Fellowship.; K.B.C. and S.G. hold NSERC Alexander Graham Bell Canada Graduate Scholarships.; This work was supported by funding from NIH (1R01HG00570 to T.R.H. and Q.D.M., R01GM084034 to K.W.L.), CIHR (MOP-49451 to T.R.H., MOP-93671 to Q.D.M., MOP-125894 to Q.D.M. and T.R.H., MOP-67011 to B.J.B., and MOP-14409 to H.D.L.), and the Intramural Program of the NIDDK (DK015602-05 to E.P.L.).; M.T.W. was funded by fellowships from CIHR and CIFAR.; We thank M. Kiledjian (PCBP1 and PCBP2), J. Stevenin (SRSF2 and SFRS7), S. Richard (QKI), M. Gorospe (TIA1), B. Chabot (SRSF9), A. Berglund (MBNL1), F. Pagani (DAZAP1), A. Bindereif (HNRNPL), M. Freeman (HNRNPK), E. Miska (LIN28A), K. Kohno (YBX1), M. Garcia-Blanco (PTBP1), R. Wharton (PUM-HD), C. Smibert (Vts1p) and M. Blanchette (Hrb27C, Hrb87F and Hrb98DE) for sending published constructs
• Keywords: SPLICING REGULATOR; GENOME-WIDE ANALYSIS; Science & Technology - Other Topics; CODE; TRANSCRIPTION FACTORS; FAMILY; PRE-MESSENGER-RNA; Science & Technology; RECOGNITION; PROTEINS; SPECIFICITIES; Multidisciplinary Sciences; REVEALS
• Research Categories: Biology, Cell; Biology, Genetics

Abstract

RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.