Abstract
Protein–RNA interactions are central to all RNA processing events, with pivotal roles in the regulation of gene expression and cellular functions. Dysregulation of these interactions has been increasingly linked to the pathogenesis of human diseases. High-throughput approaches to identify RNA-binding proteins and their binding sites on RNA — in particular, ultraviolet crosslinking followed by immunoprecipitation (CLIP) — have helped to map the RNA interactome, yielding transcriptome-wide protein–RNA atlases that have contributed to key mechanistic insights into gene expression and gene-regulatory networks. Here, we review these recent advances, explore the effects of cellular context on RNA binding, and discuss how these insights are shaping our understanding of cellular biology. We also review the potential therapeutic applications arising from new knowledge of protein–RNA interactions.
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Acknowledgements
The authors thank K. Rhine, S. Aigner, J. C. Schmok, O. Mizrahi, other members of the Yeo Lab and E. Lécuyer for helpful discussions and feedback. G.W.Y. is supported by NIH grant R01 HG004659, U24 grant HG009889 and an Allen Distinguished Investigator Award (a Paul G. Allen Frontiers Group advised grant of the Paul G. Allen Foundation). G.W.Y. is a visiting professor at the National University of Singapore. J.S.X. is supported by an NMRC OF-YIRG grant (MOH-000940).
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G.W.Y. is a co-founder and member of the Board of Directors, on the Scientific Advisory Board, equity holder and paid consultant for Eclipse BioInnovations. G.W.Y. is a visiting professor at the National University of Singapore. G.W.Y.’s interests have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. The other authors declare no competing interests.
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Xiang, J.S., Schafer, D.M., Rothamel, K.L. et al. Decoding protein–RNA interactions using CLIP-based methodologies. Nat Rev Genet (2024). https://doi.org/10.1038/s41576-024-00749-3
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DOI: https://doi.org/10.1038/s41576-024-00749-3
