Cargando…

Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans

Adenosine-to-inosine RNA editing by ADARs affects thousands of adenosines in an organism's transcriptome. However, adenosines are not edited at equal levels nor do these editing levels correlate well with ADAR expression levels. Therefore, additional mechanisms are utilized by the cell to dicta...

Descripción completa

Detalles Bibliográficos
Autores principales: Washburn, Michael C., Hundley, Heather A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836646/
https://www.ncbi.nlm.nih.gov/pubmed/26917557
http://dx.doi.org/10.1261/rna.055079.115
_version_ 1782427756789760000
author Washburn, Michael C.
Hundley, Heather A.
author_facet Washburn, Michael C.
Hundley, Heather A.
author_sort Washburn, Michael C.
collection PubMed
description Adenosine-to-inosine RNA editing by ADARs affects thousands of adenosines in an organism's transcriptome. However, adenosines are not edited at equal levels nor do these editing levels correlate well with ADAR expression levels. Therefore, additional mechanisms are utilized by the cell to dictate the editing efficiency at a given adenosine. To examine cis- and trans-acting factors that regulate A-to-I editing levels specifically in neural cells, we utilized the model organism Caenorhabditis elegans. We demonstrate that a double-stranded RNA (dsRNA) binding protein, ADR-1, inhibits editing in neurons, which is largely masked when examining editing levels from whole animals. Furthermore, expression of ADR-1 and mRNA expression of the editing target can act synergistically to regulate editing efficiency. In addition, we identify a dsRNA region within the Y75B8A.8 3′ UTR that acts as a cis-regulatory element by enhancing ADR-2 editing efficiency. Together, this work identifies mechanisms that regulate editing efficiency of noncoding A-to-I editing sites, which comprise the largest class of ADAR targets.
format Online
Article
Text
id pubmed-4836646
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-48366462017-05-01 Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans Washburn, Michael C. Hundley, Heather A. RNA Report Adenosine-to-inosine RNA editing by ADARs affects thousands of adenosines in an organism's transcriptome. However, adenosines are not edited at equal levels nor do these editing levels correlate well with ADAR expression levels. Therefore, additional mechanisms are utilized by the cell to dictate the editing efficiency at a given adenosine. To examine cis- and trans-acting factors that regulate A-to-I editing levels specifically in neural cells, we utilized the model organism Caenorhabditis elegans. We demonstrate that a double-stranded RNA (dsRNA) binding protein, ADR-1, inhibits editing in neurons, which is largely masked when examining editing levels from whole animals. Furthermore, expression of ADR-1 and mRNA expression of the editing target can act synergistically to regulate editing efficiency. In addition, we identify a dsRNA region within the Y75B8A.8 3′ UTR that acts as a cis-regulatory element by enhancing ADR-2 editing efficiency. Together, this work identifies mechanisms that regulate editing efficiency of noncoding A-to-I editing sites, which comprise the largest class of ADAR targets. Cold Spring Harbor Laboratory Press 2016-05 /pmc/articles/PMC4836646/ /pubmed/26917557 http://dx.doi.org/10.1261/rna.055079.115 Text en © 2016 Washburn and Hundley; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Report
Washburn, Michael C.
Hundley, Heather A.
Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans
title Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans
title_full Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans
title_fullStr Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans
title_full_unstemmed Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans
title_short Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans
title_sort trans and cis factors affecting a-to-i rna editing efficiency of a noncoding editing target in c. elegans
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836646/
https://www.ncbi.nlm.nih.gov/pubmed/26917557
http://dx.doi.org/10.1261/rna.055079.115
work_keys_str_mv AT washburnmichaelc transandcisfactorsaffectingatoirnaeditingefficiencyofanoncodingeditingtargetincelegans
AT hundleyheathera transandcisfactorsaffectingatoirnaeditingefficiencyofanoncodingeditingtargetincelegans