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| Home > Publications Database > Dataset: RNA Selectively Modulates Activity of Virulent Amyloid PSMα3 and Host Defense LL-37 via Phase Separation and Aggregation Dynamics, v3 |
| Home > Publications Database > Dataset: RNA Selectively Modulates Activity of Virulent Amyloid PSMα3 and Host Defense LL-37 via Phase Separation and Aggregation Dynamics, v3 |
| Dataset | DZNE-2026-00482 |
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2026
Zenodo
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Please use a persistent id in citations: doi:10.5281/zenodo.17598867 doi:10.5281/ZENODO.17598867
Abstract: Amyloids, classically linked to neurodegenerative diseases, also play critical roles in infection and immunity. Phenol-soluble modulins (PSMs) from Staphylococcus aureus are virulent amyloids that contribute to cytotoxicity, immune modulation, and biofilm stability. PSMα3 forms cross-α amyloid fibrils and shares sequence and structural features with LL-37, a human host-defense peptide that assembles into α-helical structures. Here, we uncover RNA as a potent, context-dependent modulator of their aggregation and activity. RNA consistently reduces LL-37’s cytotoxicity toward human cells without compromising its antibacterial function, suggesting a selective host-protective mechanism. In contrast, RNA preserves PSMα3’s cytotoxic and antimicrobial activity over time, likely by promoting liquid–liquid phase separation (LLPS) and stabilizing bioactive species, enabling S. aureus to fine-tune its virulence strategies. At higher concentrations, RNA drives both peptides toward distinct aggregated states, amorphous for LL-37 and fibrillar for PSMα3, underlying their divergent functional outcomes. The amyloid inhibitor EGCG abolishes the bioactivity of both PSMα3 and LL-37, counteracting RNA’s modulatory effects. Together, our findings establish RNA as a key, context-dependent modulator of both virulent amyloids and host-defense peptides, with implications for microbial immune evasion and innate immunity. Moreover, they identify phase transitions as a tunable mechanism regulating peptide bioactivity, with potential relevance for therapeutic strategies in infectious and neurodegenerative diseases.
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Dataset
Dataset: RNA Selectively Modulates Activity of Virulent Amyloid PSMα3 and Host Defense LL-37 via Phase Separation and Aggregation Dynamics, v2
Zenodo (2025) [10.5281/zenodo.17116616]
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