An aminoglycoside antibiotic drives RNA phase separation
Aminoglycoside antibiotics bind RNA with high affinity through networks of amine and hydroxyl contacts, yet whether this multivalent binding can drive macroscopic RNA phase transitions has never been tested. Here we show that neomycin B (neoB), an FDA-approved aminoglycoside, induces concentration-dependent phase separation of poly(A), poly(U), and total E.coli RNA. Condensate size and density…
Aminoglycoside antibiotics, like neomycin B, bind to RNA with great strength through various amine and hydroxyl interactions. Scientists have now demonstrated that neomycin B can cause RNA to form large-scale condensates, or clusters. The size and density of these clusters can be controlled by altering the pH and ionic strength, which in turn affect the binding of neoB and the repulsion between droplets.
When compared to spermine, another positively-charged molecule, neomycin B creates more stable condensates, even though spermine carries a similar charge at room temperature. Fucitol, which only has hydroxyl groups, does not produce the same effect. Computer simulations suggest that neoB's condensation abilities are due to extra hydrogen bonds created by its hydroxyl groups.
These findings suggest that the intricate chemical makeup of aminoglycosides, originally designed to tightly interact with RNA, can also induce macroscopic changes in RNA structure. This RNA condensation may play a role in how aminoglycosides are toxic to bacteria and damage cellular health.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
