ArticleNAR genomics and bioinformatics2023
Cooperativity boosts affinity and specificity of proteins with multiple RNA-binding domains.
Article in NAR genomics and bioinformatics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
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- Dissecting the tRNA Fragment tRF3E-Nucleolin Interaction: Implications in Breast Cancer.Biomolecules · 2025Article
- New therapeutic approaches for fibrosis: harnessing translational regulation.Trends in molecular medicine · 2025Review
- Dissecting RNA selectivity mediated by tandem RNA-binding domains.The Journal of biological chemistry · 2025Article
- Roquin exhibits opposing effects on RNA stem-loop stability through its two ROQ domain binding sites.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unraveling the Bivalent and Rapid Interactions Between a Multivalent RNA Recognition Motif and RNA: A Kinetic Approach.Biochemistry · 2024Article
- The role of structure in regulatory RNA elements.Bioscience reports · 2024Review
- Sugar-Coated: Can Multivalent Glycoconjugates Improve upon Nature's Design?Journal of the American Chemical Society · 2024Review
- High-throughput quantitation of protein-RNA UV-crosslinking efficiencies as a predictive tool for high-confidence identification of RNA-binding proteins.RNA (New York, N.Y.) · 2024Article
- Analysis of the inter-domain orientation of tandem RRM domains with diverse linkers: connecting experimental with AlphaFold2 predicted models.NAR genomics and bioinformatics · 2024Article
- Thermodynamic modeling reveals widespread multivalent binding by RNA-binding proteins.Bioinformatics (Oxford, England) · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous cellular processes rely on the binding of proteins with high affinity to specific sets of RNAs. Yet most RNA-binding domains display low specificity and affinity in comparison to DNA-binding domains. The best binding motif is typically only enriched by less than a factor 10 in high-throughput RNA SELEX or RNA bind-n-seq measurements. Here, we provide insight into how cooperative binding of multiple domains in RNA-binding proteins (RBPs) can boost their effective affinity and specificity orders of magnitude higher than their individual domains. We present a thermodynamic model to calculate the effective binding affinity (avidity) for idealized, sequence-specific RBPs with any number of RBDs given the affinities of their isolated domains. For seven proteins in which affinities for individual domains have been measured, the model predictions are in good agreement with measurements. The model also explains how a two-fold difference in binding site density on RNA can increase protein occupancy 10-fold. It is therefore rationalized that local clusters of binding motifs are the physiological binding targets of multi-domain RBPs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.