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

Charlotte Nejad, Katherine A. Pillman, Katherine J. Siddle, Geneviève Pépin, Minna Liisa Anko, Claire E. McCoy, Traude H. Beilharz, Lluís Quintana-Murci, Gregory J. Goodall, Cameron P. Bracken, Michael P. Gantier

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)332-341
Number of pages10
JournalRNA
Volume24
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Interferon
  • IsomiR
  • MicroRNA isoform
  • Stem–loop RT-qPCR
  • Taqman miRNA assays

Cite this

Nejad, Charlotte ; Pillman, Katherine A. ; Siddle, Katherine J. ; Pépin, Geneviève ; Anko, 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. In: RNA. 2018 ; Vol. 24, No. 3. pp. 332-341.
@article{beed18728d7e45bc9ec5cfdc4a5a65ad,
title = "miR-222 isoforms are differentially regulated by type-I interferon",
abstract = "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.",
keywords = "Interferon, IsomiR, MicroRNA isoform, Stem–loop RT-qPCR, Taqman miRNA assays",
author = "Charlotte Nejad and Pillman, {Katherine A.} and Siddle, {Katherine J.} and Genevi{\`e}ve P{\'e}pin and Anko, {Minna Liisa} and McCoy, {Claire E.} and Beilharz, {Traude H.} and Llu{\'i}s Quintana-Murci and Goodall, {Gregory J.} and Bracken, {Cameron P.} and Gantier, {Michael P.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1261/rna.064550.117",
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Nejad, C, Pillman, KA, Siddle, KJ, Pépin, G, Anko, ML, McCoy, CE, Beilharz, TH, Quintana-Murci, L, Goodall, GJ, Bracken, CP & Gantier, MP 2018, 'miR-222 isoforms are differentially regulated by type-I interferon' RNA, vol. 24, no. 3, pp. 332-341. https://doi.org/10.1261/rna.064550.117

miR-222 isoforms are differentially regulated by type-I interferon. / Nejad, Charlotte; Pillman, Katherine A.; Siddle, Katherine J.; Pépin, Geneviève; Anko, Minna Liisa; McCoy, Claire E.; Beilharz, Traude H.; Quintana-Murci, Lluís; Goodall, Gregory J.; Bracken, Cameron P.; Gantier, Michael P.

In: RNA, Vol. 24, No. 3, 01.03.2018, p. 332-341.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - miR-222 isoforms are differentially regulated by type-I interferon

AU - Nejad, Charlotte

AU - Pillman, Katherine A.

AU - Siddle, Katherine J.

AU - Pépin, Geneviève

AU - Anko, Minna Liisa

AU - McCoy, Claire E.

AU - Beilharz, Traude H.

AU - Quintana-Murci, Lluís

AU - Goodall, Gregory J.

AU - Bracken, Cameron P.

AU - Gantier, Michael P.

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N2 - 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.

AB - 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.

KW - Interferon

KW - IsomiR

KW - MicroRNA isoform

KW - Stem–loop RT-qPCR

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