One, Two, Three, Four! How Multiple RRMs Read the Genome Sequence
Abstract
RRM-containing proteins are involved in most of the RNA metabolism steps. Their functions are closely related to their mode of RNA recognition, which has been studied by structural biologists for more than 20 years. In this chapter, we report on high-resolution structures of single and multi RRM-RNA complexes to explain the numerous strategies used by these domains to interact specifically with a large repertoire of RNA sequences. We show that multiple variations of their canonical fold can be used to adapt to different single-stranded sequences with a large range of affinities. Furthermore, we describe the consequences on RNA binding of the different structural arrangements found in tandem RRMs and higher order RNPs. Importantly, these structures also reveal with very high accuracy the RNA motifs bound specifically by RRM-containing proteins, which correspond very often to consensus sequences identified with genome-wide approaches. Finally, we show how structural and cellular biology can benefit from each other and pave a way for understanding, defining, and predicting a code of RNA recognition by the RRMs.
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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 Afroz et al. 2015
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ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation
Bangru, S., Chen, J., Baker, N., Das, D., Chembazhi, U. V., Derham, J. M., Chorghade, S., Arif, W., Alencastro, F., Duncan, A. W., et al. (2025) · Genes & Development · doi:10.1101/gad.352129.124 · Cited by 4 · see citing works
Aazmi, O., Aswale, A. R., & Chugh, J. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.5c15374
- Authors
- Afroz, T., Cienikova, Z., Cléry, A., & Allain, F. H. T.
- Affiliations
- ETH Zurich (CH)
- Corresponding author
- Cléry, Antoine
- Allain, Frédéric H.T.
- Venue
- Methods in Enzymology
- Publisher
- Elsevier
- Published
- 2015
- Volume
- 558
- Pages
- 235-278
- ISSN
- 0076-6879 (ISSN-L)
- OpenAlex
- W2411136521
- Cited by
- 104
- References
- 7
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 12 · 2023: 10 · 2022: 12 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 19 · 2017: 8 · 2016: 4 · 2015: 2
- FWCI
- 17.64
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Methods in enzymology on CD-ROM/Methods in enzymology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Protein Structure and Dynamics
- Keywords
- RNA recognition motif, RRM domain, RNA binding, RNA-protein interactions, RNA motifs, RNA metabolism
- MeSH terms
- RNA Recognition Motif Proteins, Animals, Binding Sites, Humans, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Protein Binding, Ribonucleoproteins, RNA, Genome, Protein Structure, Secondary, Protein Structure, Tertiary, RNA Folding, Nucleotide Motifs
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