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Posttranscriptional modulation of KCNQ2 gene expression by the miR-106b microRNA family

Title
Posttranscriptional modulation of KCNQ2 gene expression by the miR-106b microRNA family
Authors
Kim, Kwon WooKim, KeetaeKim, Hee-JinKim, Byeol IBaek, MyunginSuh, Byung-Chang
DGIST Authors
Kim, Kwon Woo; Kim, Keetae; Kim, Hee-Jin; Kim, Byeol I; Baek, MyunginSuh, Byung-Chang
Issue Date
2021-11
Citation
Proceedings of the National Academy of Sciences of the United States of America, 118(47)
Type
Article
Author Keywords
KCNQ23 K+ channelmiRNAmiR-106b familyregulationKCNQ2 protein
Keywords
NEURONSEXCITABILITYSUPPRESSIONMUTATIONSITESPOTASSIUM CHANNEL SUBUNITSEPILEPSY-ASSOCIATED KCNQ2SPLICE VARIANTSHUMAN BRAIN
ISSN
0027-8424
Abstract
MicroRNAs (miRNAs) have recently emerged as important regulators of ion channel expression. We show here that select miR-106b family members repress the expression of the KCNQ2 K+ channel protein by binding to the 30-untranslated region of KCNQ2 messenger RNA. During the first few weeks after birth, the expression of miR-106b family members rapidly decreases, whereas KCNQ2 protein level inversely increases. Overexpression of miR-106b mimics resulted in a reduction in KCNQ2 protein levels. Conversely, KCNQ2 levels were up-regulated in neurons transfected with antisense miRNA inhibitors. By constructing more specific and stable forms of miR-106b controlling systems, we further confirmed that overexpression of precursor-miR-106b-5p led to a decrease in KCNQ current density and an increase in firing frequency of hippocampal neurons, while tough decoy miR-106b-5p dramatically increased current density and decreased neuronal excitability. These results unmask a regulatory mechanism of KCNQ2 channel expression in early postnatal development and hint at a role for miR-106b up-regulation in the pathophysiology of epilepsy. © 2021 National Academy of Sciences. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/15926
DOI
10.1073/pnas.2110200118
Publisher
National Academy of Sciences
Related Researcher
  • Author Suh, Byung-Chang Laboratory of Brain Signal and Synapse Research
  • Research Interests Molecular mechanisms of epilepsy and sensory pain transmission; Signaling mechanism of ion channel regulation and membrane excitability; 분자전기생리; 간질 및 통증의 분자적 기전 연구
Files:
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Collection:
Department of New BiologyCBRG(Complex Biology Research Group)1. Journal Articles
Department of Brain SciencesLocomotor NeuroCircuit Lab1. Journal Articles
Department of Brain SciencesLaboratory of Brain Signal and Synapse Research1. Journal Articles


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