An architectural role ofoskarmRNA in granule assembly

Abstract

AbstractRibonucleoprotein (RNP) granules are membraneless condensates that organize the intracellular space by compartmentalization of specific RNAs and proteins1. 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 granulesin vivoremains less explored5–7. Here, we determine the role of a sequence-specific RNA-RNA kissing-loop interaction in assembly of mesoscaleoskarRNP granules in the femaleDrosophilagermline. A two-nucleotide mutation that disrupts kissing-loop-mediatedoskarmRNA dimerization impairs condensate formationin vitro,oskargranule assembly in the developing oocyte - leading to defective posterior localization of the RNA, and abrogation ofoskar-associated processing bodies (P-bodies) upon nutritional stress. This specifictransRNA-RNA interaction acts synergistically with the scaffold RBP, Bruno8, 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.