Interspecific comparisons of the unusually long 5′ leader of the drosophila ecdysone-inducible gene E74A

The Drosophila melanogaster E74A gene is expressed in response to the steroid hormone ecdysone. Its product is a site-specific DNA-binding protein that is believed to play an important role in the normal development and metamorphosis of the fly. In addition to being under the transcriptional control of ecdysone and its receptor, there is evidence for translational regulation of the E74A mRNA. The E74A mRNA 5′ leader is unusually long (nearly 1.9 kb) and contains 17 AUGs, suggesting that translation of the mRNA would be rather inefficient. To identify features and sequences that might be important in regulating E74A translation, we determined the nucleotide sequences of the 5′ leaders from the E74A-homologous genes of D. pseudoobscura and D. virilis, comparing them to D. melanogaster. Several conserved characteristics and specific sequences were identified. In addition to conservation of the relative distances separating the three E74A gene exons encoding the 5′ leader, all three species have maintained the extensive length of the leader as well as multiple AUGs. Within the 5′ leader are numerous conserved sequences, several of which are found at the two ends of the leader and at splice site junctions, where sequence conservation might be expected. A 53-nucleotide sequence element and a 30-nucleotide element in exon 2 are highly conserved and are proposed as candidates for an internal ribosome entry site (IRES) of the E74A mRNA.