title: Natural antisense transcripts regulate the neuronal stress response and excitability.
abstract: 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.
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, United States.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Zheng
authors.forename: Vera
authors.initials: V
authors.lastname: Valakh
authors.forename: Aaron
authors.initials: A
authors.lastname: Diantonio
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Ben-Shahar
mesh_terms: D020413:3' Untranslated Regions; D000200:Action Potentials; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005838:Genotype; D018869:Heat-Shock Response; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008124:Locomotion; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D029721:Drosophila Proteins; D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels; C573946:PPK29 protein, Drosophila; D016372:RNA, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C496883:eag protein, Drosophila
keywords: DEG/ENaC; Degenerin; Drosophila; Epithelial sodium channel; fruit fly