Systematic identification of edited microRNAs in the human brain

Adenosine-to-inosine (A-to-I) editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by...

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Main Authors: Alon, Shahar, Mor, Eyal, Vigneault, Francois, Church, George M., Locatelli, Franco, Galeano, Federica, Gallo, Angela, Shomron, Noam, Eisenberg, Eli
Other Authors: Ragon Institute of MGH, MIT and Harvard
Format: Article
Language:en_US
Published: Cold Spring Harbor Laboratory Press 2013
Online Access:http://hdl.handle.net/1721.1/77148
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author Alon, Shahar
Mor, Eyal
Vigneault, Francois
Church, George M.
Locatelli, Franco
Galeano, Federica
Gallo, Angela
Shomron, Noam
Eisenberg, Eli
author2 Ragon Institute of MGH, MIT and Harvard
author_facet Ragon Institute of MGH, MIT and Harvard
Alon, Shahar
Mor, Eyal
Vigneault, Francois
Church, George M.
Locatelli, Franco
Galeano, Federica
Gallo, Angela
Shomron, Noam
Eisenberg, Eli
author_sort Alon, Shahar
collection MIT
description Adenosine-to-inosine (A-to-I) editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by A-to-I editing. Editing of miRNAs has the potential to add another layer of complexity to gene regulation pathways, especially if editing occurs within the miRNA–mRNA recognition site. Thus, it is of interest to study the extent of this phenomenon. Current reports in the literature disagree on its extent; while some reports claim that it may be widespread, others deem the reported events as rare. Utilizing a next-generation sequencing (NGS) approach supplemented by an extensive bioinformatic analysis, we were able to systematically identify A-to-I editing events in mature miRNAs derived from human brain tissues. Our algorithm successfully identified many of the known editing sites in mature miRNAs and revealed 17 novel human sites, 12 of which are in the recognition sites of the miRNAs. We confirmed most of the editing events using in vitro ADAR overexpression assays. The editing efficiency of most sites identified is very low. Similar results are obtained for publicly available data sets of mouse brain-regions tissues. Thus, we find that A-to-I editing does alter several miRNAs, but it is not widespread.
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spelling mit-1721.1/771482022-10-01T13:59:28Z Systematic identification of edited microRNAs in the human brain Alon, Shahar Mor, Eyal Vigneault, Francois Church, George M. Locatelli, Franco Galeano, Federica Gallo, Angela Shomron, Noam Eisenberg, Eli Ragon Institute of MGH, MIT and Harvard Vigneault, Francois Adenosine-to-inosine (A-to-I) editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by A-to-I editing. Editing of miRNAs has the potential to add another layer of complexity to gene regulation pathways, especially if editing occurs within the miRNA–mRNA recognition site. Thus, it is of interest to study the extent of this phenomenon. Current reports in the literature disagree on its extent; while some reports claim that it may be widespread, others deem the reported events as rare. Utilizing a next-generation sequencing (NGS) approach supplemented by an extensive bioinformatic analysis, we were able to systematically identify A-to-I editing events in mature miRNAs derived from human brain tissues. Our algorithm successfully identified many of the known editing sites in mature miRNAs and revealed 17 novel human sites, 12 of which are in the recognition sites of the miRNAs. We confirmed most of the editing events using in vitro ADAR overexpression assays. The editing efficiency of most sites identified is very low. Similar results are obtained for publicly available data sets of mouse brain-regions tissues. Thus, we find that A-to-I editing does alter several miRNAs, but it is not widespread. 2013-02-15T16:48:31Z 2013-02-15T16:48:31Z 2012-04 Article http://purl.org/eprint/type/JournalArticle 1088-9051 http://hdl.handle.net/1721.1/77148 Alon, S. et al. “Systematic Identification of Edited microRNAs in the Human Brain.” Genome Research 22.8 (2012): 1533–1540. © 2012, Published by Cold Spring Harbor Laboratory Press en_US http://dx.doi.org/10.1101/gr.131573.111 Genome Research Creative Commons Attribution Non-Commercial http://creativecommons.org/licenses/by-nc/3.0 application/pdf Cold Spring Harbor Laboratory Press Genome Research
spellingShingle Alon, Shahar
Mor, Eyal
Vigneault, Francois
Church, George M.
Locatelli, Franco
Galeano, Federica
Gallo, Angela
Shomron, Noam
Eisenberg, Eli
Systematic identification of edited microRNAs in the human brain
title Systematic identification of edited microRNAs in the human brain
title_full Systematic identification of edited microRNAs in the human brain
title_fullStr Systematic identification of edited microRNAs in the human brain
title_full_unstemmed Systematic identification of edited microRNAs in the human brain
title_short Systematic identification of edited microRNAs in the human brain
title_sort systematic identification of edited micrornas in the human brain
url http://hdl.handle.net/1721.1/77148
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