Repressor sequestration activates translation of germ granule localized mRNA

Biomolecular condensates organize and compartmentalize biochemical processes within cells1. Among these, ribonucleoprotein (RNP) granules are characterized as storage depots for translationally repressed mRNA2-8. Whether RNP granules can also activate translation and how such translation is achieved remains unclear9. This question is particularly relevant for embryonic germ granules, whose activity has been linked to germ cell fate10-13. Here, we use single-molecule imaging to show that embryonic germ cell RNP granules in Drosophila are the sites of active translation for nanos mRNA. Translating nanos mRNA is oriented with the 5end preferentially at the germ granule surface while the 3UTR is buried within the granule. Untranslated nanos mRNAs remain internal within the granule. Quantitative analysis of translational kinetics demonstrates that germ granules activate translation by antagonizing translational repression rather than changing the rate or efficiency of translation. We generated separation-of-function mutations in the disordered linker region of the scaffold protein Oskar that specifically impede nanos translation without affecting germ granule morphology or RNA localization. These mutations reveal that nanos translation is dependent on the sequestration of translational repressors within germ granules. Together, our findings show that RNP granules regulate localized protein synthesis through compartmentalized relief of translational repression raising the possibility that similar repressor-activator switches control translation in other condensates.