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

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Dominguez, Daniel, Freese, Peter, Alexis, Maria S., Su, Amanda, Hochman, Myles, Palden, Tsultrim, Bazile, Cassandra, Lambert, Nicole J. +5 more·2018·Molecular Cell
DOI 10.1016/j.molcel.2018.05.001PMC PMC6062212

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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.

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  • Linear sequence motifs alone are often insufficient to fully capture the binding specificities of RBPs, and other contextual features such as RNA secondary structure and surrounding base composition contribute to binding specificity.

    “Previous studies have shown that linear sequence motifs alone are often insufficient to fully capture the binding specificities of RBPs, and other contextual features such as RNA secondary structure and surrounding base composition contribute to binding specificity (Dominguez et al. 2018; Nostrand et al. 2020).”

    From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Dominguez et al. 2018

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Cited by

Sorted by citations

Authors
Dominguez, D., Freese, P., Alexis, M. S., Su, A., Hochman, M., Palden, T., Bazile, C., Lambert, N. J., Van Nostrand, E. L., Pratt, G. A., Yeo, G. W., Graveley, B. R., & Burge, C. B.
Affiliations
  • Massachusetts Institute of Technology (US)
  • University of California San Diego (US)
  • Agency for Science, Technology and Research (SG)
  • UConn Health (US)
Corresponding author
  • Dominguez, Daniel
  • Burge, Christopher B.
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2018-06
Volume
70
Issue
5
Pages
854-867.e9
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2018.05.001
PMC
PMC6062212
OpenAlex
W2762250455
Cited by
562
References
12
Citations by year
2026: 53 · 2025: 66 · 2024: 64 · 2023: 63 · 2022: 65 · 2021: 90 · 2020: 71 · 2019: 70 · 2018: 18 · 2017: 1 · 2016: 1
FWCI
22.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • National University of Singapore (submittedVersion)
Funders
  • NIH ENCODE Project (U54HG007005)
  • NIH (GM085319, HG004659, NS103172, HG007005)
  • National Defense Science and Engineering Graduate Fellowship
  • Rush L. Kirschstein National Research Service Award (NRSA) (12138618)
  • Burroughs Wellcome Postdoctoral Fund (027003-00001)
  • Damon Runyon Cancer Research Foundation (DRG-2172-13)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
RNA-binding proteins, RNA recognition, RNA motifs, binding specificity, RNA secondary structure, contextual features, nucleotide composition, mRNA processing
MeSH terms
RNA Recognition Motif Proteins, Base Sequence, Binding Sites, Humans, Nucleic Acid Conformation, Protein Binding, RNA, Structure-Activity Relationship, High-Throughput Nucleotide Sequencing, Nucleotide Motifs

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