Differential Requirement for Translation Initiation Factor Pathways during Ecdysone-Dependent Neuronal Remodeling in Drosophila

Cell Reports
Sandra RodeSebastian Rumpf

Abstract

Dendrite pruning of Drosophila sensory neurons during metamorphosis is induced by the steroid hormone ecdysone through a transcriptional program. In addition, ecdysone activates the eukaryotic initiation factor 4E-binding protein (4E-BP) to inhibit cap-dependent translation initiation. To uncover how efficient translation of ecdysone targets is achieved under these conditions, we assessed the requirements for translation initiation factors during dendrite pruning. We found that the canonical cap-binding complex eIF4F is dispensable for dendrite pruning, but the eIF3 complex and the helicase eIF4A are required, indicating that differential translation initiation mechanisms are operating during dendrite pruning. eIF4A and eIF3 are stringently required for translation of the ecdysone target Mical, and this depends on the 5' UTR of Mical mRNA. Functional analyses indicate that eIF4A regulates eIF3-mRNA interactions in a helicase-dependent manner. We propose that an eIF3-eIF4A-dependent alternative initiation pathway bypasses 4E-BP to ensure adequate translation of ecdysone-induced genes.

Citations

Apr 27, 2019·Acta Neuropathologica Communications·Lindsey D GoodmanNancy M Bonini
Aug 17, 2019·Learning & Memory·Ilona R Kats, Eric Klann
Mar 25, 2020·EMBO Reports·Neele WolterhoffSebastian Rumpf
Oct 6, 2020·Frontiers in Cellular Neuroscience·Erin N Lottes, Daniel N Cox
Sep 22, 2020·Trends in Genetics : TIG·Anne Ramat, Martine Simonelig
Mar 12, 2021·Wiley Interdisciplinary Reviews. RNA·J J David HoPhilip A Marsden

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