The complex and crowded cellular environment profoundly influences the structural properties and functions of biomolecules, including RNAs. In particular, biomolecular condensates represent an emerging principle for the compartmentalization of RNA and its regulation. Despite their significance, our understanding of their molecular-scale organization and effects on RNA structure remains limited. In this study, we employ atomistic simulations to investigate RNA properties in a crowded peptide environment resembling biomolecular condensates. Our findings reveal that this environment destabilizes RNA secondary structures and promotes extended nonnative conformations. Notably, the composition of peptides—specifically arginine-rich versus lysine-rich—modulates RNA behavior, suggesting that variations in condensate composition can fine-tune RNA activity in health and disease.

 
References: M. Boccalini, Y. Berezovska, G. Bussi, M. Paloni, & A. Barducci, Exploring RNA destabilization mechanisms in biomolecular condensates through atomistic simulations, Proc. Natl. Acad. Sci. U.S.A. 122 (15) e2425261122, https://doi.org/10.1073/pnas.2425261122 (2025).
 
 
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