Ec. Lai et al., The K box, a conserved 3 ' UTR sequence motif, negatively regulates accumulation of Enhancer of split Complex transcripts, DEVELOPMENT, 125(20), 1998, pp. 4077-4088
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.