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miR-222 isoforms are differentially regulated by type-I interferon

Endogenous microRNAs (miRNAs) often exist as multiple isoforms (known as “isomiRs”) with predominant variation around their 3′-end. Increasing evidence suggests that different isomiRs of the same family can have diverse functional roles, as recently demonstrated with the example of miR-222-3p 3′-end...

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Autores principales: Nejad, Charlotte, Pillman, Katherine A., Siddle, Katherine J., Pépin, Geneviève, Änkö, Minna-Liisa, McCoy, Claire E., Beilharz, Traude H., Quintana-Murci, Lluís, Goodall, Gregory J., Bracken, Cameron P., Gantier, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824353/
https://www.ncbi.nlm.nih.gov/pubmed/29263133
http://dx.doi.org/10.1261/rna.064550.117
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author Nejad, Charlotte
Pillman, Katherine A.
Siddle, Katherine J.
Pépin, Geneviève
Änkö, Minna-Liisa
McCoy, Claire E.
Beilharz, Traude H.
Quintana-Murci, Lluís
Goodall, Gregory J.
Bracken, Cameron P.
Gantier, Michael P.
author_facet Nejad, Charlotte
Pillman, Katherine A.
Siddle, Katherine J.
Pépin, Geneviève
Änkö, Minna-Liisa
McCoy, Claire E.
Beilharz, Traude H.
Quintana-Murci, Lluís
Goodall, Gregory J.
Bracken, Cameron P.
Gantier, Michael P.
author_sort Nejad, Charlotte
collection PubMed
description Endogenous microRNAs (miRNAs) often exist as multiple isoforms (known as “isomiRs”) with predominant variation around their 3′-end. Increasing evidence suggests that different isomiRs of the same family can have diverse functional roles, as recently demonstrated with the example of miR-222-3p 3′-end variants. While isomiR levels from a same miRNA family can vary between tissues and cell types, change of templated isomiR stoichiometry to stimulation has not been reported to date. Relying on small RNA-sequencing analyses, we demonstrate here that miR-222-3p 3′-end variants >23 nt are specifically decreased upon interferon (IFN) β stimulation of human fibroblasts, while shorter isoforms are spared. This length-dependent dynamic regulation of long miR-222-3p 3′-isoforms and >40 other miRNA families was confirmed in human monocyte-derived dendritic cells following infection with Salmonella Typhimurium, underlining the breadth of 3′-length regulation by infection, beyond the example of miR-222-3p. We further show that stem–loop miRNA Taqman RT-qPCR exhibits selectivity between 3′-isoforms, according to their length, and that this can lead to misinterpretation of results when these isoforms are differentially regulated. Collectively, and to our knowledge, this work constitutes the first demonstration that the stoichiometry of highly abundant templated 3′-isoforms of a same miRNA family can be dynamically regulated by a stimulus. Given that such 3′-isomiRs can have different functions, our study underlines the need to consider isomiRs when investigating miRNA-based regulation.
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spelling pubmed-58243532019-03-01 miR-222 isoforms are differentially regulated by type-I interferon Nejad, Charlotte Pillman, Katherine A. Siddle, Katherine J. Pépin, Geneviève Änkö, Minna-Liisa McCoy, Claire E. Beilharz, Traude H. Quintana-Murci, Lluís Goodall, Gregory J. Bracken, Cameron P. Gantier, Michael P. RNA Report Endogenous microRNAs (miRNAs) often exist as multiple isoforms (known as “isomiRs”) with predominant variation around their 3′-end. Increasing evidence suggests that different isomiRs of the same family can have diverse functional roles, as recently demonstrated with the example of miR-222-3p 3′-end variants. While isomiR levels from a same miRNA family can vary between tissues and cell types, change of templated isomiR stoichiometry to stimulation has not been reported to date. Relying on small RNA-sequencing analyses, we demonstrate here that miR-222-3p 3′-end variants >23 nt are specifically decreased upon interferon (IFN) β stimulation of human fibroblasts, while shorter isoforms are spared. This length-dependent dynamic regulation of long miR-222-3p 3′-isoforms and >40 other miRNA families was confirmed in human monocyte-derived dendritic cells following infection with Salmonella Typhimurium, underlining the breadth of 3′-length regulation by infection, beyond the example of miR-222-3p. We further show that stem–loop miRNA Taqman RT-qPCR exhibits selectivity between 3′-isoforms, according to their length, and that this can lead to misinterpretation of results when these isoforms are differentially regulated. Collectively, and to our knowledge, this work constitutes the first demonstration that the stoichiometry of highly abundant templated 3′-isoforms of a same miRNA family can be dynamically regulated by a stimulus. Given that such 3′-isomiRs can have different functions, our study underlines the need to consider isomiRs when investigating miRNA-based regulation. Cold Spring Harbor Laboratory Press 2018-03 /pmc/articles/PMC5824353/ /pubmed/29263133 http://dx.doi.org/10.1261/rna.064550.117 Text en © 2018 Nejad et al.; 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
Nejad, Charlotte
Pillman, Katherine A.
Siddle, Katherine J.
Pépin, Geneviève
Änkö, Minna-Liisa
McCoy, Claire E.
Beilharz, Traude H.
Quintana-Murci, Lluís
Goodall, Gregory J.
Bracken, Cameron P.
Gantier, Michael P.
miR-222 isoforms are differentially regulated by type-I interferon
title miR-222 isoforms are differentially regulated by type-I interferon
title_full miR-222 isoforms are differentially regulated by type-I interferon
title_fullStr miR-222 isoforms are differentially regulated by type-I interferon
title_full_unstemmed miR-222 isoforms are differentially regulated by type-I interferon
title_short miR-222 isoforms are differentially regulated by type-I interferon
title_sort mir-222 isoforms are differentially regulated by type-i interferon
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824353/
https://www.ncbi.nlm.nih.gov/pubmed/29263133
http://dx.doi.org/10.1261/rna.064550.117
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