Translational Control of Autophagy by Orb in the Drosophila Germline

Dev Cell. 2015 Dec 7;35(5):622-631. doi: 10.1016/j.devcel.2015.11.003. Epub 2015 Nov 25.

Abstract

Drosophila Orb, the homolog of vertebrate CPEB, is a key translational regulator involved in oocyte polarity and maturation through poly(A) tail elongation of specific mRNAs. orb also has an essential function during early oogenesis that has not been addressed at the molecular level. Here, we show that orb prevents cell death during early oogenesis, thus allowing oogenesis to progress. It does so through the repression of autophagy by directly repressing, together with the CCR4 deadenylase, the translation of Autophagy-specific gene 12 (Atg12) mRNA. Autophagy and cell death observed in orb mutant ovaries are reduced by decreasing Atg12 or other Atg mRNA levels. These results reveal a role of Orb in translational repression and identify autophagy as an essential pathway regulated by Orb during early oogenesis. Importantly, they also establish translational regulation as a major mode of control of autophagy, a key process in cell homeostasis in response to environmental cues.

Keywords: Atg genes; CPEB; autophagy; cell death; deadenylation; germline; orb; translational control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Autophagy-Related Protein-1 Homolog
  • Cell Cycle
  • Cell Death
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Developmental*
  • Germ Cells / metabolism
  • Homeostasis
  • Immunoprecipitation
  • Mutation
  • Oocytes / metabolism
  • Oogenesis
  • Ovary / metabolism
  • Protein Biosynthesis
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribonucleases / metabolism

Substances

  • Drosophila Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • orb protein, Drosophila
  • Atg1 protein, Drosophila
  • Autophagy-Related Protein-1 Homolog
  • Protein-Serine-Threonine Kinases
  • CCR4 protein, Drosophila
  • Ribonucleases

Associated data

  • GEO/GSE74476