Cited by 314RNA Research and SplicingRNA and protein synthesis mechanismsRNA regulation and disease

Sequence-specific binding of single-stranded RNA: is there a code for recognition?

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Auweter, Sigrid D., Oberstrass, Florian C., Allain, Frédéric H.-T.·2006·Nucleic Acids Research

Abstract

A code predicting the RNA sequence that will be bound by a certain protein based on its amino acid sequence or its structure would provide a useful tool for the design of RNA binders with desired sequence-specificity. Such de novo designed RNA binders could be of extraordinary use in both medical and basic research applications. Furthermore, a code could help to predict the cellular functions of RNA-binding proteins that have not yet been extensively studied. A comparative analysis of Pumilio homology domains, zinc-containing RNA binders, hnRNP K homology domains and RNA recognition motifs is performed in this review. Based on this, a set of binding rules is proposed that hints towards a code for RNA recognition by these domains. Furthermore, we discuss the intermolecular interactions that are important for RNA binding and summarize their importance in providing affinity and specificity.

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  • Proteins with a single RNA binding domain (RBD) are believed to interact with three to five contiguous RNA bases, whereas proteins with multiple RBDs can interact with bipartite motifs separated by one or more bases, where the two cores in bipartite motifs are bound by distinct RBDs within the same protein.

    “Proteins with a single RNA binding domain (RBD) are believed to interact with three to five contiguous RNA bases, whereas proteins with multiple RBDs can interact with bipartite motifs separated by one or more bases, where the two cores in bipartite motifs are bound by distinct RBDs within the same protein (Auweter et al. 2006; Afroz et al. 2015).”

    From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Auweter et al. 2006

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  • Canonical RBDs typically bind short single-stranded RNA sequences, but some also recognize structured RNAs.

    “Canonical RBDs typically bind short, single-stranded (ss)RNA sequences3,4, but some also recognize structured RNAs5.”
  • Inference by simple protein identity is particularly valuable for RBPs for which it may not be possible to derive recognition codes.

    “Nonetheless, inference by simple protein identity is particularly valuable for those RBPs for which it may not be possible to derive recognition codes5.”

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Authors
Auweter, S. D., Oberstrass, F. C., & Allain, F. H.-T.
Affiliations
ETH Zurich (CH)
Corresponding author
Allain, Frédéric H.-T.
Venue
Nucleic Acids Research
Published
2006-09-18
Volume
34
Issue
17
Pages
4943-4959
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2020433571
Cited by
314
References
90
Citations by year
2026: 7 · 2025: 11 · 2024: 16 · 2023: 15 · 2022: 7 · 2021: 11 · 2020: 11 · 2019: 10 · 2018: 17 · 2017: 14 · 2016: 11 · 2015: 16 · 2014: 26 · 2013: 15 · 2012: 29
FWCI
1.30
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed (publishedVersion)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc)
  • ETH Zürich Research Collection
Funders
  • National Science Foundation
  • University of Southern California
  • Florida State University
  • University of Oxford
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • Eidgenössische Technische Hochschule Zürich
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, sequence-specific RNA binding, RNA recognition motif, binding specificity, binding affinity, intermolecular interactions
MeSH terms
Base Sequence, Binding Sites, Models, Molecular, Protein Binding, RNA, Protein Engineering, RNA-Binding Proteins, Protein Structure, Tertiary

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