Repression of Gurken translation by a meiotic checkpoint in Drosophila oogenesis is suppressed by a reduction in the dose of eIF1A.

TitleRepression of Gurken translation by a meiotic checkpoint in Drosophila oogenesis is suppressed by a reduction in the dose of eIF1A.
Publication TypeJournal Article
Year of Publication2014
AuthorsLi, W, Klovstad, M, Schüpbach, T
JournalDevelopment
Volume141
Issue20
Pagination3910-21
Date Published2014 Oct
ISSN1477-9129
KeywordsAnimals, DNA Damage, Drosophila melanogaster, Drosophila Proteins, Egg Proteins, Eukaryotic Initiation Factor-1, Female, Gene Expression Regulation, Developmental, Genotype, Male, Meiosis, Mutation, Oocytes, Oogenesis, Ovary, Phenotype, Polyribosomes, Protein Biosynthesis, Ribonucleoproteins, RNA, Messenger, Transforming Growth Factor alpha
Abstract

<p>In Drosophila melanogaster, the anteroposterior (AP) and dorsoventral (DV) axes of the oocyte and future embryo are established through the localization and translational regulation of gurken (grk) mRNA. This process involves binding of specific factors to the RNA during transport and a dynamic remodeling of the grk-containing ribonucleoprotein (RNP) complexes once they have reached their destination within the oocyte. In ovaries of spindle-class females, an activated DNA damage checkpoint causes inefficient Grk translation and ventralization of the oocyte. In a screen for modifiers of the oocyte DV patterning defects, we identified a mutation in the eIF1A gene as a dominant suppressor. We show that reducing the function of eIF1A in spnB ovaries suppresses the ventralized eggshell phenotype by restoring Grk expression. This suppression is not the result of more efficient DNA damage repair or of disrupted checkpoint activation, but is coupled to an increase in the amount of grk mRNA associated with polysomes. In spnB ovaries, the activated meiotic checkpoint blocks Grk translation by disrupting the accumulation of grk mRNA in a translationally competent RNP complex that contains the translational activator Oo18 RNA-binding protein (Orb); this regulation involves the translational repressor Squid (Sqd). We further propose that reduction of eIF1A allows more efficient Grk translation possibly because of the presence of specific structural features in the grk 5'UTR. </p>

DOI10.1242/dev.109306
Alternate JournalDevelopment
PubMed ID25231760
PubMed Central IDPMC4197705
Grant ListR01 GM077620 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States