Neurons regulate ionic fluxes across their plasma membrane to maintain their 
excitable properties under varying environmental conditions. However, the 
mechanisms that regulate ion channels abundance remain poorly understood. Here 
we show that pickpocket 29 (ppk29), a gene that encodes a Drosophila 
degenerin/epithelial sodium channel (DEG/ENaC), regulates neuronal excitability 
via a protein-independent mechanism. We demonstrate that the mRNA 3'UTR of ppk29 
affects neuronal firing rates and associated heat-induced seizures by acting as 
a natural antisense transcript (NAT) that regulates the neuronal mRNA levels of 
seizure (sei), the Drosophila homolog of the human Ether-à-go-go Related Gene 
(hERG) potassium channel. We find that the regulatory impact of ppk29 mRNA on 
sei is independent of the sodium channel it encodes. Thus, our studies reveal a 
novel mRNA dependent mechanism for the regulation of neuronal excitability that 
is independent of protein-coding capacity. DOI: 
http://dx.doi.org/10.7554/eLife.01849.001.