TY - JOUR T1 - The <em>Drosophila</em> Eukaryotic Initiation Factor eIF6 affects development by regulating apoptosis via the ecdysone pathway JF - bioRxiv DO - 10.1101/201558 SP - 201558 AU - Arianna Russo AU - Guido Gatti AU - Roberta Alfieri AU - Elisa Pesce AU - Kelly Soanes AU - Sara Ricciardi AU - Cristina Cheroni AU - Thomas Vaccari AU - Stefano Biffo AU - Piera Calamita Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/10/11/201558.abstract N2 - Translation factors downregulation modulates gene expression but the effect of their overexpression is still unknown. The Eukaryotic Initiation Factor 6 (eIF6) is necessary for ribosome biogenesis and translation initiation. The eif6 gene is a single genetic locus highly conserved from yeast to humans indicating a tight regulation of its gene dosage. eIF6 haploinsufficiency protects mice from lymphomagenesis, and eIF6 is upregulated or amplified in some cancers, but a mechanistic study on the effects of eIF6 overexpression is still lacking. Taking advantage of genetic tractability of D. melanogaster, we characterized the first in vivo model of eIF6 upregulation. Drosophila eIF6 overexpression increases translation and results in a rough eye phenotype due to aberrant apoptosis. Mechanistically, eIF6 reshapes transcription and histone acetylation, disrupting the ecdysone network. This work is the first evidence of how increased translation generates a full transcriptional and hormonal dysregulation, providing new perspectives on the physiological relevance of the translational machinery in regulating gene expression and a model to screen drugs potentially useful to treat cells with altered eif6 gene dosage. ER -