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A compendium of RNA-binding motifs for decoding gene regulation

Author

Listed:
  • 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
    Present address: Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Rheumatology and Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA.)

  • Hamed S. Najafabadi

    (Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
    University of Toronto, Toronto M5S 3G4, 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
    University of Toronto, Toronto M5S 1A8, Canada)

  • Benjamin J. Blencowe

    (Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
    University of Toronto, Toronto M5S 1A8, Canada)

  • Quaid D. Morris

    (Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
    University of Toronto, Toronto M5S 2E4, Canada
    University of Toronto, Toronto M5S 1A8, Canada
    University of Toronto, Toronto M5S 3G4, Canada)

  • Timothy R. Hughes

    (Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada
    University of Toronto, Toronto M5S 1A8, Canada)

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.

Suggested Citation

  • 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 & R, 2013. "A compendium of RNA-binding motifs for decoding gene regulation," Nature, Nature, vol. 499(7457), pages 172-177, July.
  • Handle: RePEc:nat:nature:v:499:y:2013:i:7457:d:10.1038_nature12311
    DOI: 10.1038/nature12311
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    Cited by:

    1. Xuan Ye & Wen Yang & Soon Yi & Yanan Zhao & Gabriele Varani & Eckhard Jankowsky & Fan Yang, 2023. "Two distinct binding modes provide the RNA-binding protein RbFox with extraordinary sequence specificity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Komal Soni & Pravin Kumar Ankush Jagtap & Santiago Martínez-Lumbreras & Sophie Bonnal & Arie Geerlof & Ralf Stehle & Bernd Simon & Juan Valcárcel & Michael Sattler, 2023. "Structural basis for specific RNA recognition by the alternative splicing factor RBM5," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Aidan M. Fenix & Yuichiro Miyaoka & Alessandro Bertero & Steven M. Blue & Matthew J. Spindler & Kenneth K. B. Tan & Juan A. Perez-Bermejo & Amanda H. Chan & Steven J. Mayerl & Trieu D. Nguyen & Caitli, 2021. "Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Siddharth Sethi & David Zhang & Sebastian Guelfi & Zhongbo Chen & Sonia Garcia-Ruiz & Emmanuel O. Olagbaju & Mina Ryten & Harpreet Saini & Juan A. Botia, 2022. "Leveraging omic features with F3UTER enables identification of unannotated 3’UTRs for synaptic genes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Christoph Sadée & Lauren D. Hagler & Winston R. Becker & Inga Jarmoskaite & Pavanapuresan P. Vaidyanathan & Sarah K. Denny & William J. Greenleaf & Daniel Herschlag, 2022. "A comprehensive thermodynamic model for RNA binding by the Saccharomyces cerevisiae Pumilio protein PUF4," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Ulrike Zinnall & Miha Milek & Igor Minia & Carlos H. Vieira-Vieira & Simon Müller & Guido Mastrobuoni & Orsalia-Georgia Hazapis & Simone Giudice & David Schwefel & Nadine Bley & Franka Voigt & Jeffrey, 2022. "HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    7. Seisuke Yamashita & Kozo Tomita, 2023. "Mechanism of U6 snRNA oligouridylation by human TUT1," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    8. Seungjae Lee & Yen-Chung Chen & Austin E. Gillen & J. Matthew Taliaferro & Bart Deplancke & Hongjie Li & Eric C. Lai, 2022. "Diverse cell-specific patterns of alternative polyadenylation in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Huijuan Feng & Xiang-Jun Lu & Suvrajit Maji & Linxi Liu & Dmytro Ustianenko & Noam D. Rudnick & Chaolin Zhang, 2024. "Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Maya Ron & Igor Ulitsky, 2022. "Context-specific effects of sequence elements on subcellular localization of linear and circular RNAs," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Diane Lefaudeux & Supriya Sen & Kevin Jiang & Alexander Hoffmann, 2022. "Kinetics of mRNA nuclear export regulate innate immune response gene expression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Deivid C. Rodrigues & Marat Mufteev & Kyoko E. Yuki & Ashrut Narula & Wei Wei & Alina Piekna & Jiajie Liu & Peter Pasceri & Olivia S. Rissland & Michael D. Wilson & James Ellis, 2023. "Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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