The K box, a conserved 3 ' UTR sequence motif, negatively regulates accumulation of Enhancer of split Complex transcripts

Cell-cell interactions mediated by the Notch receptor play an essential rol e in the development of the Drosophila adult peripheral nervous system (PNS ), Transcriptional activation of multiple genes of the Enhancer of split Co mplex [E(spl)-C] is a key intracellular response to Notch receptor activity . Here we report that most E(spl)-C genes contain a novel sequence motif, t he K box (TGTGAT), in their 3' untranslated regions (3' UTRs), We present t hree lines of evidence that demonstrate the importance of this element in t he post-transcriptional regulation of E(spl)-C genes. First, K box sequence s are specifically conserved in the orthologs of two structurally distinct E(spl)-C genes (m4 and m8) from a distantly related Drosophila species. Sec ond, the wild-type m8 3' UTR strongly reduces accumulation of heterologous transcripts in vivo, an activity that requires its K box sequences. Finally , m8 genomic DNA transgenes lacking these motifs cause mild gain-of-functio n PNS defects and can partially phenocopy the genetic interaction of E(spl) (D) with Notch(spl). Although E(spl)-C genes are expressed in temporally an d spatially specific patterns, we find that K box-mediated regulation is ub iquitous, implying that other targets of this activity may exist. In suppor t of this, we present sequence analyses that implicate genes of the iroquoi s Complex (Iro-C) and engrailed as additional targets of K box-mediated reg ulation.