[1] Donnelly Centre, [2] Department of Computer Science, [3] Department of Molecular Genetics, [4] Department of Electrical and Computer Engineering, University of Toronto
[5] Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
[6] Department of Medicine, Perelman School of Medicine at the University of Pennsylvania
[7] Department of Biochemistry, Emory University School of Medicine
[8] Department of Biology and Center for Genomics and Systems Biology, New York University
[9] Department of Pharmacology, School of Medicine and Public Health, University of Wisconsin-Madison
[10] Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio
[#] Current address: Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Rheumatology and Biomedical Informatics, Cincinnati Children's Hospital Medical Center
[*] These authors made equal contributions to the manuscript.
[**] Communicating authors:
and
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.