Molecular mechanisms of biomolecular condensate formation in Drosophila melanogaster siRNA biogenesis.

ABSTRACT: Biogenesis of small interfering RNAs (siRNA) in Drosophila melanogaster involves the processing of double-stranded RNA (dsRNA) by Dcr-2 with Loqs-PD/R2D2 and Ago2. Here, we show that Loqs-PD and Ago2 are found in biomolecular condensates in vivo and display liquid-liquid phase separation in vitro. The phase separation of Loqs-PD depends on the RNA-binding capability of its double-stranded RNA-binding domains and is further modulated by the preceding N-terminal region. An intrinsically disordered region in Ago2 (Ago2IDR) forms condensates in the presence of RNA in vitro. Combining NMR spectroscopy and mutational analysis, we show that Ago2IDR/RNA condensates are fluid, with significant polypeptide backbone flexibility, and are stabilized by a dense network of interactions involving arginine

SUBMITTER: Hipp C 

PROVIDER: S-EPMC12276012 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature