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Regulated RNA Editing and Functional Epistasis in Shaker Potassium Channels

Regulated point modification by an RNA editing enzyme occurs at four conserved sites in the Drosophila Shaker potassium channel. Single mRNA molecules can potentially represent any of 2(4) = 16 permutations (isoforms) of these natural variants. We generated isoform expression profiles to assess sexu...

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Detalles Bibliográficos
Autores principales: Ingleby, Lindsey, Maloney, Rachel, Jepson, James, Horn, Richard, Reenan, Robert
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606942/
https://www.ncbi.nlm.nih.gov/pubmed/19114634
http://dx.doi.org/10.1085/jgp.200810133
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author Ingleby, Lindsey
Maloney, Rachel
Jepson, James
Horn, Richard
Reenan, Robert
author_facet Ingleby, Lindsey
Maloney, Rachel
Jepson, James
Horn, Richard
Reenan, Robert
author_sort Ingleby, Lindsey
collection PubMed
description Regulated point modification by an RNA editing enzyme occurs at four conserved sites in the Drosophila Shaker potassium channel. Single mRNA molecules can potentially represent any of 2(4) = 16 permutations (isoforms) of these natural variants. We generated isoform expression profiles to assess sexually dimorphic, spatial, and temporal differences. Striking tissue-specific expression was seen for particular isoforms. Moreover, isoform distributions showed evidence for coupling (linkage) of editing sites. Genetic manipulations of editing enzyme activity demonstrated that a chief determinant of Shaker editing site choice resides not in the editing enzyme, but rather, in unknown factors intrinsic to cells. Characterizing the biophysical properties of currents in nine isoforms revealed an unprecedented feature, functional epistasis; biophysical phenotypes of isoforms cannot be explained simply by the consequences of individual editing effects at the four sites. Our results unmask allosteric communication across disparate regions of the channel protein and between evolved and regulated amino acid changes introduced by RNA editing.
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spelling pubmed-26069422009-07-01 Regulated RNA Editing and Functional Epistasis in Shaker Potassium Channels Ingleby, Lindsey Maloney, Rachel Jepson, James Horn, Richard Reenan, Robert J Gen Physiol Articles Regulated point modification by an RNA editing enzyme occurs at four conserved sites in the Drosophila Shaker potassium channel. Single mRNA molecules can potentially represent any of 2(4) = 16 permutations (isoforms) of these natural variants. We generated isoform expression profiles to assess sexually dimorphic, spatial, and temporal differences. Striking tissue-specific expression was seen for particular isoforms. Moreover, isoform distributions showed evidence for coupling (linkage) of editing sites. Genetic manipulations of editing enzyme activity demonstrated that a chief determinant of Shaker editing site choice resides not in the editing enzyme, but rather, in unknown factors intrinsic to cells. Characterizing the biophysical properties of currents in nine isoforms revealed an unprecedented feature, functional epistasis; biophysical phenotypes of isoforms cannot be explained simply by the consequences of individual editing effects at the four sites. Our results unmask allosteric communication across disparate regions of the channel protein and between evolved and regulated amino acid changes introduced by RNA editing. The Rockefeller University Press 2009-01 /pmc/articles/PMC2606942/ /pubmed/19114634 http://dx.doi.org/10.1085/jgp.200810133 Text en © 2009 Ingleby et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Ingleby, Lindsey
Maloney, Rachel
Jepson, James
Horn, Richard
Reenan, Robert
Regulated RNA Editing and Functional Epistasis in Shaker Potassium Channels
title Regulated RNA Editing and Functional Epistasis in Shaker Potassium Channels
title_full Regulated RNA Editing and Functional Epistasis in Shaker Potassium Channels
title_fullStr Regulated RNA Editing and Functional Epistasis in Shaker Potassium Channels
title_full_unstemmed Regulated RNA Editing and Functional Epistasis in Shaker Potassium Channels
title_short Regulated RNA Editing and Functional Epistasis in Shaker Potassium Channels
title_sort regulated rna editing and functional epistasis in shaker potassium channels
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606942/
https://www.ncbi.nlm.nih.gov/pubmed/19114634
http://dx.doi.org/10.1085/jgp.200810133
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