A Large-Scale Binding and Functional Map of Human RNA Binding Proteins

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Abstract

Abstract Genomes encompass all the information necessary to specify the development and function of an organism. In addition to genes, genomes also contain a myriad of functional elements that control various steps in gene expression. A major class of these elements function only when transcribed into RNA as they serve as the binding sites for RNA binding proteins (RBPs), which act to control post-transcriptional processes including splicing, cleavage and polyadenylation, RNA editing, RNA localization, stability, and translation. Despite the importance of these functional RNA elements encoded in the genome, they have been much less studied than genes and DNA elements. Here, we describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. These data expand the catalog of functional elements encoded in the human genome by addition of a large set of elements that function at the RNA level through interaction with RBPs. Highlights 223 eCLIP datasets for 150 RBPs reveal a wide variety of in vivo RNA target classes. 472 knockdown/RNA-seq profiles of 263 RBPs reveal factor-responsive targets and integration with eCLIP indicates RNA expression and splicing regulatory patterns. 78 RNA Bind-N-Seq profiles of in vitro binding motifs reveal links between in vitro and in vivo binding and indicate that eCLIP peaks that contain in vitro motifs are more strongly associated with regulation. 274 maps of RBP subcellular localization by immunofluorescence indicate widespread organelle-specific RNA processing regulation. 63 ChIP-seq profiles of DNA association suggest broad interconnectivity between chromatin association and RNA processing.

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