137: Rethinking RNA-binding proteins: riboregulation beyond the classics

Hentze MW et al., Cell - A review that examines the expansion of the RNA-binding proteome, evaluates evidence for many non-canonical RBPs, and highlights riboregulation as an emerging mechanism by which RNA controls protein function, complexes, and metabolism. Key terms: RNA-binding proteins, non-canonical RBPs, riboregulation, intrinsically disordered regions, RNA interactome. Study Highlights:Large-scale UV crosslinking and proteomic approaches have dramatically expanded the catalogue of RNA-binding proteins to include many non-canonical, well-studied proteins that lack classical RNA-binding domains. Mapping efforts show that IDRs and nucleotide cofactor-binding folds frequently mediate these interactions, and validated examples reveal RNA can regulate protein-protein interactions, enzymatic activity, complex assembly, and transmembrane import. Representative cases include IRP1, GAPDH, ENO1, SHMT1, p62/vtRNA1-1, and lncRNA/circRNA regulators of metabolic enzymes and signaling complexes. The authors emphasize the need for orthogonal validation, high-resolution structures, and in vivo functional studies to distinguish biologically relevant riboregulation from methodological artifacts. Conclusion:Riboregulation extends RNA function beyond classical targets: many non-canonical RBPs engage RNA via IDRs or metabolic folds and RNA can directly modulate protein activity, interactions, and assemblies; rigorous validation and structural work are essential to define mechanism and relevance for physiology and disease. Music:Enjoy the music based on this article at the end of the episode. Article title:Rethinking RNA-binding proteins: Riboregulation challenges prevailing views First author:Hentze MW Journal:Cell DOI:10.1016/j.cell.2025.06.021 Reference:Hentze MW, Sommerkamp P, Ravi V, Gebauer F. Rethinking RNA-binding proteins: Riboregulation challenges prevailing views. Cell. 2025;188:4811-4827. https://doi.org/10.1016/j.cell.2025.06.021 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/rethinking-rna-binding-proteins-riboregulation-challenges-prevailing-views QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-09-14. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the narration's depiction of riboregulation concepts, non-canonical RBPs, validation methods (UV crosslinking, RIC/eRIC, OOPS/PTex, EU labeling, PLA, NMR), IDRs and Rossmann-fold binding surfaces, and functional examples (P62/vtRNA1-1, SHMT1, ENO1, metabolon formation with GlycoLINC, ATP5A1 import), plus virolo- transcript topics: Riboregulation concept and paradigm shift; Non-canonical RNA-binding proteins (RBPs) and loss of classical RBDs; Validation technologies for RNA–protein interactions (UV crosslinking, RIC/eRIC, OOPS/PTex, EU labeling, PLA, NMR); IDRs as RNA-binding surfaces and Rossmann-fold cofactor pockets; Functional mechanisms: allostery, oligomerization, metabolon scaffolding; Specific riboregulation examples: P62/vtRNA1-1, SHMT1, ENO1,...