A compendium of RNA-binding motifs for decoding gene regulation

Debashish Ray, Hilal Kazan, Kate B. Cook, Matthew T. Weirauch, Hamed S. Najafabadi, Xiao Li, Serge Gueroussov, Mihai Albu, Hong Zheng, Ally Yang, Hong Na, Manuel Irimia, Leah H. Matzat, Ryan K. Dale, Sarah A. Smith, Christopher A. Yarosh, Seth M. Kelly, Behnam Nabet, Desirea Mecenas, Weimin Li, Rakesh S. Laishram, Mei Qiao, Howard D. Lipshitz, Fabio Piano, Anita H. Corbett, Russ P. Carstens, Brendan J. Frey, Richard A. Anderson, Kristen W. Lynch, Luiz O. F. Penalva, Elissa P. Lei, Andrew G. Fraser, Benjamin J. Blencowe, Quaid D. Morris () and Timothy R. Hughes ()
Additional contact information
Debashish Ray: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Hilal Kazan: University of Toronto, Toronto M5S 2E4, Canada
Kate B. Cook: University of Toronto, Toronto M5S 1A8, Canada
Matthew T. Weirauch: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Hamed S. Najafabadi: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Xiao Li: University of Toronto, Toronto M5S 1A8, Canada
Serge Gueroussov: University of Toronto, Toronto M5S 1A8, Canada
Mihai Albu: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Hong Zheng: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Ally Yang: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Hong Na: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Manuel Irimia: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Leah H. Matzat: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Ryan K. Dale: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Sarah A. Smith: Perelman School of Medicine at the University of Pennsylvania
Christopher A. Yarosh: Perelman School of Medicine at the University of Pennsylvania
Seth M. Kelly: Emory University School of Medicine
Behnam Nabet: Perelman School of Medicine at the University of Pennsylvania
Desirea Mecenas: New York University
Weimin Li: Molecular and Cellular Pharmacology Program, School of Medicine and Public Health, University of Wisconsin-Madison
Rakesh S. Laishram: Molecular and Cellular Pharmacology Program, School of Medicine and Public Health, University of Wisconsin-Madison
Mei Qiao: Children’s Cancer Research Institute, UTHSCSA
Howard D. Lipshitz: University of Toronto, Toronto M5S 1A8, Canada
Fabio Piano: New York University
Anita H. Corbett: Emory University School of Medicine
Russ P. Carstens: Perelman School of Medicine at the University of Pennsylvania
Brendan J. Frey: University of Toronto, Toronto M5S 3G4, Canada
Richard A. Anderson: Molecular and Cellular Pharmacology Program, School of Medicine and Public Health, University of Wisconsin-Madison
Kristen W. Lynch: Perelman School of Medicine at the University of Pennsylvania
Luiz O. F. Penalva: Children’s Cancer Research Institute, UTHSCSA
Elissa P. Lei: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Andrew G. Fraser: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Benjamin J. Blencowe: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Quaid D. Morris: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
Timothy R. Hughes: Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada

Nature, 2013, vol. 499, issue 7457, 172-177

Abstract: 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.

Date: 2013
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DOI: 10.1038/nature12311

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