An architectural role of oskar mRNA in granule assembly

Ribonucleoprotein (RNP) granules are membraneless condensates that organize the intracellular space by compartmentalization of specific RNAs and proteins ¹ . Studies have shown that RNA tunes the phase behavior of RNA binding proteins (RBPs) ^2–4 , but the role of intermolecular RNA-RNA interactions in assembly of RNP granules in vivo remains less explored ^5–7 . Here, we determine the role of a sequence-specific RNA-RNA kissing-loop interaction in assembly of mesoscale oskar RNP granules in the female Drosophila germline. A two-nucleotide mutation that disrupts kissing-loop-mediated oskar mRNA dimerization impairs condensate formation in vitro , oskar granule assembly in the developing oocyte - leading to defective posterior localization of the RNA, and abrogation of oskar -associated processing bodies (P-bodies) upon nutritional stress. This specific trans RNA-RNA interaction acts synergistically with the scaffold RBP, Bruno ⁸ , in driving condensate assembly. Our study highlights the architectural contribution of an mRNA and its specific secondary structure and tertiary interactions in formation of an RNP granule essential for embryonic development.