A compendium of RNA-binding motifs for decoding gene regulation

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. This study reports a global analysis of binding sites for over 200 RNA-binding proteins (RBPs) from 24 species; conserved RNA-binding motifs are identified, and their analysis allows prediction of interaction sites based on the sequence of the RNA-binding domain alone. The sequence and context of RNA that dictate the interaction of RNA-binding proteins with their targets have tended to be studied on a protein-by-protein basis. A study by Timothy Hughes and colleagues now reports a global analysis of binding sites for more than 200 RNA-binding proteins from 24 eukaryote species. Conserved RNA-binding motifs are identified, and their analysis allows for the prediction of interaction sites on the basis of the RNA-binding domain sequence alone. The motifs also are found to reflect each molecule's function, which will aid in understanding the roles of previously uncharacterized examples.