Augmented prediction of multi-species protein–RNA interactions using evolutionary conservation of RNA-binding proteins
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Abstract
RNA-binding proteins (RBPs) play critical roles in the regulation of gene expression. Recent studies have begun to detail the RNA recognition mechanisms of diverse RBPs. However, given the array of RBPs studied so far, it is implausible to experimentally profile RBP-binding peaks for hundreds of RBPs in multiple non-model organisms. Here, we introduce MuSIC ( Mu lti- S pecies RBP–RNA I nteractions using C onservation), a deep learning-based framework for predicting cross-species RBP–RNA interactions by leveraging label smoothing and evolutionary conservation of RBPs across 11 phylogenetically diverse species ranging from human to yeast. MuSIC outperforms state-of-the-art computational methods, and achieves highly accurate prediction of RBP-binding peaks across species. The prediction confidence is higher in the metazoan species, partially reflecting differences in RBP conservation patterns. Finally, the effects of homologous genetic variants on RBP binding can be computationally quantified across species, followed by experimental validations. The target transcripts with disrupted binding events are enriched in the ubiquitination-associated pathways. To summarize, MuSIC provides a useful computational framework for predicting RBP–RNA interactions cross-species and quantifying the effects of genetic variants on RBP binding, offering insights into the RBP-mediated regulatory mechanisms implicated in human diseases.
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Harris, S. E., Alexis, M. S., Giri, G., Cavazos, F. F., Hu, Y., Murn, J., Aleman, M. M., Burge, C. B., & Dominguez, D. (2024) · Nature Communications · doi:10.1038/s41467-024-52231-7 · Cited by 10 · see citing works
DeepProtein: deep learning library and benchmark for protein sequence learning
Xie, J., Li, Y., & Fu, T. (2025) · Bioinformatics · doi:10.1093/bioinformatics/btaf165 · Cited by 10 · see citing works
Self-citationde Sompele, S. V., Pécheux, L., Couso, J., Meunier, A., Sánchez, M., & Baere, E. B. W. D. (2017) · Scientific Reports · doi:10.1038/s41598-017-18326-6 · Cited by 8 · see citing works
RNAFlow: RNA Structure & Sequence Design via Inverse Folding-Based Flow MatchingPreprint
Nori, D., & Jin, W. (2024) · arXiv (Cornell University) · doi:10.48550/arxiv.2405.18768 · Cited by 6 · see citing works
Hu, L., Xie, G., Wu, Y., Li, Y., Wan, Z.-L., Li, M., Wang, J., & Wang, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.13.642977 · Cited by 1 · see citing works
Self-citation
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- Authors
- He, J., Zhou, T., Hu, L.-F., Jiao, Y., Wang, J., Yan, S., Jia, S., Chen, Q., Zhu, W., Zhang, J., Jia, M., Li, Y., Wang, X., Wang, Y., Yang, Y. T., & Sun, L.
- Affiliations
- Shandong University (CN)
- Peking University (CN)
- City University of Hong Kong (HK)
- Fudan University (CN)
- Corresponding author
- Yang, Yucheng T.
- Sun, Lei
- ORCID
- Venue
- Nature Communications
- Published
- 2026-04-27
- Volume
- 17
- Issue
- 1
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W4414584279
- Cited by
- 0
- References
- 95
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- CityU Scholars (submittedVersion, cc-by)
- Funders
- Shandong University
- Qingdao Postdoctoral Science Foundation (NO. QDBSH20240102200)
- National Natural Science Foundation of China (32300521, 32422013, 82341086, 32025007, No.32422013, No.82341086, No.32025007, No.32300521)
- Natural Science Foundation of Shandong Province (ZR2025QA09)
- Postdoctoral Innovation Project of Shandong Province (NO. SDCX-ZG-202400146)
- 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 › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- RNA-binding proteins, RBP-RNA interactions, cross-species prediction, evolutionary conservation, label smoothing, deep learning, single nucleotide variants, ubiquitination, gene expression regulation, non-model organisms
- MeSH terms
- Animals, Binding Sites, Humans, Phylogeny, Protein Binding, RNA, RNA-Binding Proteins, Conserved Sequence, Evolution, Molecular, Computational Biology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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