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Adenosine to Inosine editing frequency controlled by splicing efficiency

Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon–intron basepairing, mRNA splicing...

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Autores principales: Licht, Konstantin, Kapoor, Utkarsh, Mayrhofer, Elisa, Jantsch, Michael F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291252/
https://www.ncbi.nlm.nih.gov/pubmed/27112566
http://dx.doi.org/10.1093/nar/gkw325
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author Licht, Konstantin
Kapoor, Utkarsh
Mayrhofer, Elisa
Jantsch, Michael F.
author_facet Licht, Konstantin
Kapoor, Utkarsh
Mayrhofer, Elisa
Jantsch, Michael F.
author_sort Licht, Konstantin
collection PubMed
description Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon–intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates. We demonstrate for the first time that the extent of editing is controlled by splicing kinetics when editing is guided by intronic elements. In contrast, editing sites that are exclusively defined by exonic structures are almost unaffected by the splicing efficiency of nearby introns. In addition, we show that editing levels in pre- and mature mRNAs do not match. This phenomenon can in part be explained by the editing state of an RNA influencing its splicing rate but also by the binding of the editing enzyme ADAR that interferes with splicing.
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spelling pubmed-52912522017-02-10 Adenosine to Inosine editing frequency controlled by splicing efficiency Licht, Konstantin Kapoor, Utkarsh Mayrhofer, Elisa Jantsch, Michael F. Nucleic Acids Res RNA Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon–intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates. We demonstrate for the first time that the extent of editing is controlled by splicing kinetics when editing is guided by intronic elements. In contrast, editing sites that are exclusively defined by exonic structures are almost unaffected by the splicing efficiency of nearby introns. In addition, we show that editing levels in pre- and mature mRNAs do not match. This phenomenon can in part be explained by the editing state of an RNA influencing its splicing rate but also by the binding of the editing enzyme ADAR that interferes with splicing. Oxford University Press 2016-07-27 2016-04-25 /pmc/articles/PMC5291252/ /pubmed/27112566 http://dx.doi.org/10.1093/nar/gkw325 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle RNA
Licht, Konstantin
Kapoor, Utkarsh
Mayrhofer, Elisa
Jantsch, Michael F.
Adenosine to Inosine editing frequency controlled by splicing efficiency
title Adenosine to Inosine editing frequency controlled by splicing efficiency
title_full Adenosine to Inosine editing frequency controlled by splicing efficiency
title_fullStr Adenosine to Inosine editing frequency controlled by splicing efficiency
title_full_unstemmed Adenosine to Inosine editing frequency controlled by splicing efficiency
title_short Adenosine to Inosine editing frequency controlled by splicing efficiency
title_sort adenosine to inosine editing frequency controlled by splicing efficiency
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291252/
https://www.ncbi.nlm.nih.gov/pubmed/27112566
http://dx.doi.org/10.1093/nar/gkw325
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