miR-222 isoforms are differentially regulated by type-I interferon
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(Published version)
Date
2018
Authors
Nejad, C.
Pillman, K.
Siddle, K.
Pépin, G.
Anko, M.
McCoy, C.
Beilharz, T.
Quintana-Murci, L.
Goodall, G.
Bracken, C.
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Journal article
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RNA: A publication of the RNA Society, 2018; 24(3):332-341
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Charlotte Nejad, Katherine A. Pillman, Katherine J. Siddle, Geneviève Pépin, Minna-Liisa Änkö, Claire E. McCoy, Traude H. Beilharz, Lluís Quintana-Murci, Gregory J. Goodall, Cameron P. Bracken and Michael P. Gantier
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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.
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Data source: Supplementary material, https://doi.org/10.1261/rna.064550.117
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© 2018 Nejad et al. This article is distributed exclusively by theRNASociety 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/.