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@MISC{Rayan:282945,
author = {Rayan, Bader and Barnea, Eilon and Indig, Rinat and
Pantoja, Christian Felipe and Gayk, Jesse and Lupu-Haber,
Yael and Upcher, Alexander and Argoetti, Amir and Larsen,
Jacob and Buell, Alexander and Zweckstetter, Markus and
Landau, Meytal},
title = {{D}ataset: {RNA} {S}electively {M}odulates {A}ctivity of
{V}irulent {A}myloid {PSM}α3 and {H}ost {D}efense {LL}-37
via {P}hase {S}eparation and {A}ggregation {D}ynamics, v2},
publisher = {Zenodo},
reportid = {DZNE-2025-01406},
year = {2025},
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 fibrillar polymorphs, 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, overriding RNA’s modulatory effects.
Together, our findings establish RNA as a key modulator of
both virulent amyloids and host-defense peptides, with broad
implications for microbial immune evasion, innate immunity,
and amyloid-associated diseases. Moreover, they highlight
phase transitions as a tunable mechanism for regulating
peptide bioactivity and a promising therapeutic target
across infectious and neurodegenerative conditions.},
cin = {AG Zweckstetter},
cid = {I:(DE-2719)1410001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)32},
doi = {10.5281/zenodo.17116616},
url = {https://pub.dzne.de/record/282945},
}