Sequence, Structure, and Context Preferences of Human RNA Binding Proteins
Author(s)
Freese, Peter; Alexis, Maria S.; Van Nostrand, Eric L.; Pratt, Gabriel A.; Yeo, Gene W.; Graveley, Brenton R.; Dominguez, Daniel; Su, Amanda J; Hochman, Myles; Palden, Tsultrim; Bazile, Cassandra; Lambert, Nicole; Burge, Christopher B; ... Show more Show less
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RNA binding proteins (RBPs) orchestrate the production, processing, and function of mRNAs. Here, we present the affinity landscapes of 78 human RBPs using an unbiased assay that determines the sequence, structure, and context preferences of these proteins in vitro by deep sequencing of bound RNAs. These data enable construction of “RNA maps” of RBP activity without requiring crosslinking-based assays. We found an unexpectedly low diversity of RNA motifs, implying frequent convergence of binding specificity toward a relatively small set of RNA motifs, many with low compositional complexity. Offsetting this trend, however, we observed extensive preferences for contextual features distinct from short linear RNA motifs, including spaced “bipartite” motifs, biased flanking nucleotide composition, and bias away from or toward RNA structure. Our results emphasize the importance of contextual features in RNA recognition, which likely enable targeting of distinct subsets of transcripts by different RBPs that recognize the same linear motif. Dominguez et al. describe in vitro binding specificities of 78 human RNA binding proteins (RBPs) to RNA sequences and structures. They find that many RBPs bind similar RNA motifs but differ in affinity for spaced “bipartite” motifs, flanking composition, and RNA structure, supporting the model that distinct motif occurrences are often discriminated based on sequence context. Keywords: alternative splicing; mRNA stability; RBNS; RNA binding protein; RNA recognition motif;
KH domain; zinc finger; Pum domain; RNA secondary structure; RNA context
Date issued
2018-06Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of BiologyJournal
Molecular Cell
Publisher
Elsevier
Citation
Dominguez, Daniel et al. “Sequence, Structure, and Context Preferences of Human RNA Binding Proteins.” Molecular Cell 70, 5 (June 2018): 854–867 © 2018 The Authors
Version: Final published version
ISSN
1097-2765
1097-4164