[PDF][PDF] Sequence, structure, and context preferences of human RNA binding proteins

D Dominguez, P Freese, MS Alexis, A Su, M Hochman… - Molecular cell, 2018 - cell.com
D Dominguez, P Freese, MS Alexis, A Su, M Hochman, T Palden, C Bazile, NJ Lambert…
Molecular cell, 2018cell.com
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 …
Summary
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.
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