Selective translational control refines cell-type specific responses to the steroid hormone ecdysone. Robert Ihry, Arash Bashirullah. Sch Pharmacy, Univ Wisconsin, Madison, Madison, WI.

   Steroid hormones elicit a wide range of biological responses by directly regulating transcription. Here we show that selective translational control plays a critical role in refining steroid-dependent transcriptional responses in Drosophila. We show that the DEAD box RNA helicase belle, directly regulates translation of the ets transcription factor E74A. E74A transcription is directly and ubiquitously induced by the steroid hormone ecdysone; in contrast, translation of E74A mRNA is restricted to a subset of cells. We demonstrate that the distribution of E74A protein expression is determined by cell-type specific regulation of belle-dependent translation. Belle protein is ubiquitously expressed, indicating that belle function is itself regulated in a cell-type specific manner. Using forward genetic approaches we have identified several genes required for belle-dependent translation, genes that have not been previously implicated in translational control. Given that the human homolog of belle (DDX3) plays a critical role in tumorigenesis and in HIV infections, this belle-dependent pathway outlines a novel and critical regulatory network.