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

Russo, Arianna, Gatti, Guido, Alfieri, Roberta, Pesce, Elisa, Soanes, Kelly, Ricciardi, Sara, Mancino, Marilena, Cheroni, Cristina, Vaccari, Thomas, Biffo, Stefano, Calamita, Piera
Developmental biology 2019 v.455 no.1 pp. 100-111
Drosophila melanogaster, biochemical pathways, biogenesis, biosynthesis, cell proliferation, ecdysone, genes, mammals, models, phenotype, programmed cell death, protein synthesis, ribosomes, signal transduction, transcription factors, yeasts
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.