title: A role for Drosophila dFoxO and dFoxO 5'UTR internal ribosomal entry sites during fasting.
abstract: One way animals may cope with nutrient deprivation is to broadly repress translation by inhibiting 5'-cap initiation. However, under these conditions specific proteins remain essential to survival during fasting. Such peptides may be translated through initiation at 5'UTR Internal Ribosome Entry Sites (IRES). Here we show that the Drosophila melanogaster Forkhead box type O (dFoxO) transcription factor is required for adult survival during fasting, and that the 5'UTR of dfoxO has the ability to initiate IRES-mediated translation in cell culture. Previous work has shown that insulin negatively regulates dFoxO through AKT-mediated phosphorylation while dFoxO itself induces transcription of the insulin receptor dInR, which also harbors IRES. Here we report that IRES-mediated translation of both dFoxO and dInR is activated in fasted Drosophila S2 cells at a time when cap-dependent translation is reduced. IRES mediated translation of dFoxO and dInR may be essential to ensure function and sensitivity of the insulin signaling pathway during fasting.
authors.affiliation: Department of Ecology and Evolutionary Biology, Brown University, Providence, Rhode Island, United States of America. eugenia_villa-cuesta@brown.edu
authors.forename: Eugenia
authors.initials: E
authors.lastname: Villa-Cuesta
authors.forename: Brian T
authors.initials: BT
authors.lastname: Sage
authors.forename: Marc
authors.initials: M
authors.lastname: Tatar
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D011972:Receptor, Insulin