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

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. [Display omitted] •Dendrite pruning in the fly PNS requires eIF4A and eIF3, but not eIF4E/G•The helicase eIF4A and eIF3 cooperate for expression of the ecdysone target Mical•Initiation pathway choice depends on signals in the Mical 5′ UTR•eIF3 and eIF4A seem to be linked to several ecdysone-induced processes Ecdysone regulates developmental neurite pruning in Drosophila through the activation of pruning genes, but it also negatively affects global translation rate. Rode et al. find that these effects are coordinated at the level of translation initiation, as pruning genes use the eIF3 initiation complex instead of the ecdysone-sensitive canonical eIF4F complex.