Natural antisense transcripts regulate the neuronal stress response and excitability

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 d...

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Main Authors: Xingguo Zheng, Vera Valakh, Aaron DiAntonio, Yehuda Ben-Shahar
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2014-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/01849
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author Xingguo Zheng
Vera Valakh
Aaron DiAntonio
Yehuda Ben-Shahar
author_facet Xingguo Zheng
Vera Valakh
Aaron DiAntonio
Yehuda Ben-Shahar
author_sort Xingguo Zheng
collection DOAJ
description 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.
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spelling doaj.art-eea61016b00f4b49a52771217eb4fa282022-12-22T03:24:27ZengeLife Sciences Publications LtdeLife2050-084X2014-03-01310.7554/eLife.01849Natural antisense transcripts regulate the neuronal stress response and excitabilityXingguo Zheng0Vera Valakh1Aaron DiAntonio2Yehuda Ben-Shahar3Department of Biology, Washington University in St. Louis, St. Louis, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United States; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, United StatesDepartment of Biology, Washington University in St. Louis, St. Louis, United StatesNeurons 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.https://elifesciences.org/articles/01849DegenerinEpithelial sodium channelDEG/ENaCDrosophilafruit fly
spellingShingle Xingguo Zheng
Vera Valakh
Aaron DiAntonio
Yehuda Ben-Shahar
Natural antisense transcripts regulate the neuronal stress response and excitability
eLife
Degenerin
Epithelial sodium channel
DEG/ENaC
Drosophila
fruit fly
title Natural antisense transcripts regulate the neuronal stress response and excitability
title_full Natural antisense transcripts regulate the neuronal stress response and excitability
title_fullStr Natural antisense transcripts regulate the neuronal stress response and excitability
title_full_unstemmed Natural antisense transcripts regulate the neuronal stress response and excitability
title_short Natural antisense transcripts regulate the neuronal stress response and excitability
title_sort natural antisense transcripts regulate the neuronal stress response and excitability
topic Degenerin
Epithelial sodium channel
DEG/ENaC
Drosophila
fruit fly
url https://elifesciences.org/articles/01849
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AT veravalakh naturalantisensetranscriptsregulatetheneuronalstressresponseandexcitability
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AT yehudabenshahar naturalantisensetranscriptsregulatetheneuronalstressresponseandexcitability