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A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression

A-to-I RNA editing is a conserved widespread phenomenon in which adenosine (A) is converted to inosine (I) by adenosine deaminases (ADARs) in double-stranded RNA regions, mainly noncoding. Mutations in ADAR enzymes in Caenorhabditis elegans cause defects in normal development but are not lethal as i...

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Autores principales: Goldstein, Boaz, Agranat-Tamir, Lily, Light, Dean, Ben-Naim Zgayer, Orna, Fishman, Alla, Lamm, Ayelet T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340973/
https://www.ncbi.nlm.nih.gov/pubmed/28031250
http://dx.doi.org/10.1101/gr.211169.116
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author Goldstein, Boaz
Agranat-Tamir, Lily
Light, Dean
Ben-Naim Zgayer, Orna
Fishman, Alla
Lamm, Ayelet T.
author_facet Goldstein, Boaz
Agranat-Tamir, Lily
Light, Dean
Ben-Naim Zgayer, Orna
Fishman, Alla
Lamm, Ayelet T.
author_sort Goldstein, Boaz
collection PubMed
description A-to-I RNA editing is a conserved widespread phenomenon in which adenosine (A) is converted to inosine (I) by adenosine deaminases (ADARs) in double-stranded RNA regions, mainly noncoding. Mutations in ADAR enzymes in Caenorhabditis elegans cause defects in normal development but are not lethal as in human and mouse. Previous studies in C. elegans indicated competition between RNA interference (RNAi) and RNA editing mechanisms, based on the observation that worms that lack both mechanisms do not exhibit defects, in contrast to the developmental defects observed when only RNA editing is absent. To study the effects of RNA editing on gene expression and function, we established a novel screen that enabled us to identify thousands of RNA editing sites in nonrepetitive regions in the genome. These include dozens of genes that are edited at their 3′ UTR region. We found that these genes are mainly germline and neuronal genes, and that they are down-regulated in the absence of ADAR enzymes. Moreover, we discovered that almost half of these genes are edited in a developmental-specific manner, indicating that RNA editing is a highly regulated process. We found that many pseudogenes and other lncRNAs are also extensively down-regulated in the absence of ADARs in the embryo but not in the fourth larval (L4) stage. This down-regulation is not observed upon additional knockout of RNAi. Furthermore, levels of siRNAs aligned to pseudogenes in ADAR mutants are enhanced. Taken together, our results suggest a role for RNA editing in normal growth and development by regulating silencing via RNAi.
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spelling pubmed-53409732017-09-01 A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression Goldstein, Boaz Agranat-Tamir, Lily Light, Dean Ben-Naim Zgayer, Orna Fishman, Alla Lamm, Ayelet T. Genome Res Research A-to-I RNA editing is a conserved widespread phenomenon in which adenosine (A) is converted to inosine (I) by adenosine deaminases (ADARs) in double-stranded RNA regions, mainly noncoding. Mutations in ADAR enzymes in Caenorhabditis elegans cause defects in normal development but are not lethal as in human and mouse. Previous studies in C. elegans indicated competition between RNA interference (RNAi) and RNA editing mechanisms, based on the observation that worms that lack both mechanisms do not exhibit defects, in contrast to the developmental defects observed when only RNA editing is absent. To study the effects of RNA editing on gene expression and function, we established a novel screen that enabled us to identify thousands of RNA editing sites in nonrepetitive regions in the genome. These include dozens of genes that are edited at their 3′ UTR region. We found that these genes are mainly germline and neuronal genes, and that they are down-regulated in the absence of ADAR enzymes. Moreover, we discovered that almost half of these genes are edited in a developmental-specific manner, indicating that RNA editing is a highly regulated process. We found that many pseudogenes and other lncRNAs are also extensively down-regulated in the absence of ADARs in the embryo but not in the fourth larval (L4) stage. This down-regulation is not observed upon additional knockout of RNAi. Furthermore, levels of siRNAs aligned to pseudogenes in ADAR mutants are enhanced. Taken together, our results suggest a role for RNA editing in normal growth and development by regulating silencing via RNAi. Cold Spring Harbor Laboratory Press 2017-03 /pmc/articles/PMC5340973/ /pubmed/28031250 http://dx.doi.org/10.1101/gr.211169.116 Text en © 2017 Goldstein et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six 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 Research
Goldstein, Boaz
Agranat-Tamir, Lily
Light, Dean
Ben-Naim Zgayer, Orna
Fishman, Alla
Lamm, Ayelet T.
A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression
title A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression
title_full A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression
title_fullStr A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression
title_full_unstemmed A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression
title_short A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression
title_sort a-to-i rna editing promotes developmental stage–specific gene and lncrna expression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340973/
https://www.ncbi.nlm.nih.gov/pubmed/28031250
http://dx.doi.org/10.1101/gr.211169.116
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