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 3' 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.
Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Marina
M
Chekulaeva
Matthias W
MW
Hentze
Anne
A
Ephrussi
D020413:3' Untranslated Regions; D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005260:Female; D017344:Genes, Insect; D066298:In Vitro Techniques; D009690:Nucleic Acid Conformation; D009865:Oocytes / Q000378:metabolism; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
D020413:3' Untranslated Regions; D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C093437:bru1 protein, Drosophila; C105238:cup protein, Drosophila; C091675:osk protein, Drosophila