Role for para sodium channel gene 3′ UTR in the modification of Drosophila seizure susceptibility

Abstract

Voltage-gated sodium channel genes are highly regulated at the level of transcription or translation. In this study, we have utilized the combination of genetic, electrophysiological, and molecular analyses to identify a 7-kb 3'-untranslated region (UTR) of the Drosophila para sodium channel gene. Disruption of this segment by P-element insertion causes reduction of para primary transcript, but not Rbp2 transcripts. The identification of this novel 3'-UTR is based on a P-insertion mutation called para(JS1), which was isolated from a P-element mutagenesis screen for seizure suppressors in a Drosophila model of epilepsy. The para(JS1) mutation was identified 6845 bp downstream of the para gene, which resides in an intergenic region that lies between para and Rbp2 (RNA-binding protein 2) genes. Interestingly, reverse-transcription PCR showed that the region containing para(JS1) is substantially transcribed and this transcribed region is associated with para coding region. We discussed possible mechanisms of how reduced transcription of the para gene or alterations in sodium channel subunit composition might be indicated by the para(JS1) mutation and implications for para 3' UTR function.