Bruno Acts as a Dual Repressor of oskar Translation, Promoting mRNA Oligomerization and Formation of Silencing Particles

Prior to reaching the posterior pole of the Drosophila oocyte, oskar mRNA is translationally silenced by Bruno binding to BREs in the 3ʹ untranslated region. The eIF4E binding protein Cup interacts with Bruno and inhibits oskar translation. Validating current models, we directly demonstrate the mechanism proposed for Cup-mediated repression: inhibition of small ribosomal subunit recruitment to oskar mRNA. However, 43S complex recruitment remains inhibited in the absence of functional Cup, uncovering a second Bruno-dependent silencing mechanism. This mechanism involves mRNA oligomerization and formation of large (50S-80S) silencing particles that cannot be accessed by ribosomes. Bruno-dependent mRNA oligomerization into silencing particles emerges as a mode of translational control that may be particularly suited to coupling with mRNA transport.