Modulating eIF6 levels unveils the role of translation in ecdysone biosynthesis during Drosophila development

Dev Biol. 2019 Nov 1;455(1):100-111. doi: 10.1016/j.ydbio.2019.05.013. Epub 2019 Jul 5.

Abstract

During development, ribosome biogenesis and translation reach peak activities, due to impetuous cell proliferation. Current models predict that protein synthesis elevation is controlled by transcription factors and signalling pathways. Developmental models addressing translation factors overexpression effects are lacking. Eukaryotic Initiation Factor 6 (eIF6) is necessary for ribosome biogenesis and efficient translation. eIF6 is a single gene, conserved from yeasts to mammals, suggesting a tight regulation need. We generated a Drosophila melanogaster model of eIF6 upregulation, leading to a boost in general translation and the shut-down of the ecdysone biosynthetic pathway. Indeed, translation modulation in S2 cells showed that translational rate and ecdysone biosynthesis are inversely correlated. In vivo, eIF6-driven alterations delayed Programmed Cell Death (PCD), resulting in aberrant phenotypes, partially rescued by ecdysone administration. Our data show that eIF6 triggers a translation program with far-reaching effects on metabolism and development, stressing the driving and central role of translation.

Keywords: 20HE; Drosophila development; Ecdysone; Translation; eIF6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apoptosis / genetics
  • Cell Line
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Ecdysone / biosynthesis*
  • Gene Expression Regulation, Developmental*
  • Imaginal Discs / growth & development
  • Imaginal Discs / metabolism
  • Peptide Initiation Factors / genetics*
  • Peptide Initiation Factors / metabolism
  • Protein Biosynthesis / genetics*
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Drosophila Proteins
  • Peptide Initiation Factors
  • Transcription Factors
  • eIF-6
  • Ecdysone