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Mol Cell. 2018 Jun 7;70(5):854-867.e9. doi: 10.1016/j.molcel.2018.05.001. Epub 2018 Jun 7.

Sequence, Structure, and Context Preferences of Human RNA Binding Proteins.

Author information

1
Department of Biology, MIT, Cambridge, MA, USA. Electronic address: didoming@mit.edu.
2
Program in Computational and Systems Biology, MIT, Cambridge, MA, USA.
3
Department of Biology, MIT, Cambridge, MA, USA.
4
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
5
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA; Bioinformatics and Systems Biology Graduate Program, University of California at San Diego, La Jolla, CA, USA.
6
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Molecular Engineering Laboratory, A(∗)STAR, Singapore, Singapore.
7
Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health, Farmington, CT, USA.
8
Department of Biology, MIT, Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA. Electronic address: cburge@mit.edu.

Abstract

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.

KEYWORDS:

KH domain; Pum domain; RBNS; RNA binding protein; RNA context; RNA recognition motif; RNA secondary structure; alternative splicing; mRNA stability; zinc finger

PMID:
29883606
PMCID:
PMC6062212
[Available on 2019-06-07]
DOI:
10.1016/j.molcel.2018.05.001
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