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Biomolecular Condensates Can Enhance Pathological RNA Clustering. | LitMetric

AI Article Synopsis

  • The study investigates how biomolecular condensates, which are clusters of proteins and nucleic acids, influence the clustering of repeat expanded RNAs linked to neurological disorders, revealing a phenomenon called age-dependent percolation transition.* -
  • The research shows that these RNAs form nanoscale clusters within the condensates, leading to structures with a solid RNA-rich core and a fluid RNA-depleted shell, driven by specific RNA sequence features and stability.* -
  • Findings emphasize the protective role of RNA-binding proteins like G3BP1, which can prevent excessive RNA clustering within these condensates, suggesting a potential strategy to mitigate aberrant RNA phase transitions in neurological diseases.*

Article Abstract

Intracellular aggregation of repeat expanded RNA has been implicated in many neurological disorders. Here, we study the role of biomolecular condensates on irreversible RNA clustering. We find that physiologically relevant and disease-associated repeat RNAs spontaneously undergo an age-dependent percolation transition inside multi-component protein-nucleic acid condensates to form nanoscale clusters. Homotypic RNA clusters drive the emergence of multiphasic condensate structures with an RNA-rich solid core surrounded by an RNA-depleted fluid shell. The timescale of the RNA clustering, which drives a liquid-to-solid transition of biomolecular condensates, is determined by the sequence features, stability of RNA secondary structure, and repeat length. Importantly, G3BP1, the core scaffold of stress granules, introduces heterotypic buffering to homotypic RNA-RNA interactions and impedes intra-condensate RNA clustering in an ATP-independent manner. Our work suggests that biomolecular condensates can act as sites for RNA aggregation. It also highlights the functional role of RNA-binding proteins in suppressing aberrant RNA phase transitions.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195159PMC
http://dx.doi.org/10.1101/2024.06.11.598371DOI Listing

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