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Complex regulation of ADAR-mediated RNA-editing across tissues

BACKGROUND: RNA-editing is a tightly regulated, and essential cellular process for a properly functioning brain. Dysfunction of A-to-I RNA editing can have catastrophic effects, particularly in the central nervous system. Thus, understanding how the process of RNA-editing is regulated has important...

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Autores principales: Huntley, Melanie A., Lou, Melanie, Goldstein, Leonard D., Lawrence, Michael, Dijkgraaf, Gerrit J.P., Kaminker, Joshua S., Gentleman, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714477/
https://www.ncbi.nlm.nih.gov/pubmed/26768488
http://dx.doi.org/10.1186/s12864-015-2291-9
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author Huntley, Melanie A.
Lou, Melanie
Goldstein, Leonard D.
Lawrence, Michael
Dijkgraaf, Gerrit J.P.
Kaminker, Joshua S.
Gentleman, Robert
author_facet Huntley, Melanie A.
Lou, Melanie
Goldstein, Leonard D.
Lawrence, Michael
Dijkgraaf, Gerrit J.P.
Kaminker, Joshua S.
Gentleman, Robert
author_sort Huntley, Melanie A.
collection PubMed
description BACKGROUND: RNA-editing is a tightly regulated, and essential cellular process for a properly functioning brain. Dysfunction of A-to-I RNA editing can have catastrophic effects, particularly in the central nervous system. Thus, understanding how the process of RNA-editing is regulated has important implications for human health. However, at present, very little is known about the regulation of editing across tissues, and individuals. RESULTS: Here we present an analysis of RNA-editing patterns from 9 different tissues harvested from a single mouse. For comparison, we also analyzed data for 5 of these tissues harvested from 15 additional animals. We find that tissue specificity of editing largely reflects differential expression of substrate transcripts across tissues. We identified a surprising enrichment of editing in intronic regions of brain transcripts, that could account for previously reported higher levels of editing in brain. There exists a small but remarkable amount of editing which is tissue-specific, despite comparable expression levels of the edit site across multiple tissues. Expression levels of editing enzymes and their isoforms can explain some, but not all of this variation. CONCLUSIONS: Together, these data suggest a complex regulation of the RNA-editing process beyond transcript expression levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2291-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-47144772016-01-16 Complex regulation of ADAR-mediated RNA-editing across tissues Huntley, Melanie A. Lou, Melanie Goldstein, Leonard D. Lawrence, Michael Dijkgraaf, Gerrit J.P. Kaminker, Joshua S. Gentleman, Robert BMC Genomics Research Article BACKGROUND: RNA-editing is a tightly regulated, and essential cellular process for a properly functioning brain. Dysfunction of A-to-I RNA editing can have catastrophic effects, particularly in the central nervous system. Thus, understanding how the process of RNA-editing is regulated has important implications for human health. However, at present, very little is known about the regulation of editing across tissues, and individuals. RESULTS: Here we present an analysis of RNA-editing patterns from 9 different tissues harvested from a single mouse. For comparison, we also analyzed data for 5 of these tissues harvested from 15 additional animals. We find that tissue specificity of editing largely reflects differential expression of substrate transcripts across tissues. We identified a surprising enrichment of editing in intronic regions of brain transcripts, that could account for previously reported higher levels of editing in brain. There exists a small but remarkable amount of editing which is tissue-specific, despite comparable expression levels of the edit site across multiple tissues. Expression levels of editing enzymes and their isoforms can explain some, but not all of this variation. CONCLUSIONS: Together, these data suggest a complex regulation of the RNA-editing process beyond transcript expression levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2291-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-15 /pmc/articles/PMC4714477/ /pubmed/26768488 http://dx.doi.org/10.1186/s12864-015-2291-9 Text en © Huntley et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Huntley, Melanie A.
Lou, Melanie
Goldstein, Leonard D.
Lawrence, Michael
Dijkgraaf, Gerrit J.P.
Kaminker, Joshua S.
Gentleman, Robert
Complex regulation of ADAR-mediated RNA-editing across tissues
title Complex regulation of ADAR-mediated RNA-editing across tissues
title_full Complex regulation of ADAR-mediated RNA-editing across tissues
title_fullStr Complex regulation of ADAR-mediated RNA-editing across tissues
title_full_unstemmed Complex regulation of ADAR-mediated RNA-editing across tissues
title_short Complex regulation of ADAR-mediated RNA-editing across tissues
title_sort complex regulation of adar-mediated rna-editing across tissues
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714477/
https://www.ncbi.nlm.nih.gov/pubmed/26768488
http://dx.doi.org/10.1186/s12864-015-2291-9
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