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Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis

BACKGROUND: MicroRNAs (miRNAs) belong to a class of evolutionary conserved, non-coding small RNAs with regulatory functions on gene expression. They negatively affect the expression of target genes by promoting either RNA degradation or translational inhibition. In recent years, converging studies h...

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Autores principales: Ma, Qin, Matsunaga, Atsuko, Ho, Brenda, Oksenberg, Jorge R., Didonna, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552381/
https://www.ncbi.nlm.nih.gov/pubmed/33046105
http://dx.doi.org/10.1186/s12974-020-01964-5
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author Ma, Qin
Matsunaga, Atsuko
Ho, Brenda
Oksenberg, Jorge R.
Didonna, Alessandro
author_facet Ma, Qin
Matsunaga, Atsuko
Ho, Brenda
Oksenberg, Jorge R.
Didonna, Alessandro
author_sort Ma, Qin
collection PubMed
description BACKGROUND: MicroRNAs (miRNAs) belong to a class of evolutionary conserved, non-coding small RNAs with regulatory functions on gene expression. They negatively affect the expression of target genes by promoting either RNA degradation or translational inhibition. In recent years, converging studies have identified miRNAs as key regulators of oligodendrocyte (OL) functions. OLs are the cells responsible for the formation and maintenance of myelin in the central nervous system (CNS) and represent a principal target of the autoimmune injury in multiple sclerosis (MS). METHODS: MiRAP is a novel cell-specific miRNA affinity-purification technique which relies on genetically tagging Argonaut 2 (AGO2), an enzyme involved in miRNA processing. Here, we exploited miRAP potentiality to characterize OL-specific miRNA dynamics in the MS model experimental autoimmune encephalomyelitis (EAE). RESULTS: We show that 20 miRNAs are differentially regulated in OLs upon transition from pre-symptomatic EAE stages to disease peak. Subsequent in vitro differentiation experiments demonstrated that a sub-group of them affects the OL maturation process, mediating either protective or detrimental signals. Lastly, transcriptome profiling highlighted the endocytosis, ferroptosis, and FoxO cascades as the pathways associated with miRNAs mediating or inhibiting OL maturation. CONCLUSIONS: Altogether, our work supports a dual role for miRNAs in autoimmune demyelination. In particular, the enrichment in miRNAs mediating pro-myelinating signals suggests an active involvement of these non-coding RNAs in the homeostatic response toward neuroinflammatory injury.
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spelling pubmed-75523812020-10-13 Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis Ma, Qin Matsunaga, Atsuko Ho, Brenda Oksenberg, Jorge R. Didonna, Alessandro J Neuroinflammation Research BACKGROUND: MicroRNAs (miRNAs) belong to a class of evolutionary conserved, non-coding small RNAs with regulatory functions on gene expression. They negatively affect the expression of target genes by promoting either RNA degradation or translational inhibition. In recent years, converging studies have identified miRNAs as key regulators of oligodendrocyte (OL) functions. OLs are the cells responsible for the formation and maintenance of myelin in the central nervous system (CNS) and represent a principal target of the autoimmune injury in multiple sclerosis (MS). METHODS: MiRAP is a novel cell-specific miRNA affinity-purification technique which relies on genetically tagging Argonaut 2 (AGO2), an enzyme involved in miRNA processing. Here, we exploited miRAP potentiality to characterize OL-specific miRNA dynamics in the MS model experimental autoimmune encephalomyelitis (EAE). RESULTS: We show that 20 miRNAs are differentially regulated in OLs upon transition from pre-symptomatic EAE stages to disease peak. Subsequent in vitro differentiation experiments demonstrated that a sub-group of them affects the OL maturation process, mediating either protective or detrimental signals. Lastly, transcriptome profiling highlighted the endocytosis, ferroptosis, and FoxO cascades as the pathways associated with miRNAs mediating or inhibiting OL maturation. CONCLUSIONS: Altogether, our work supports a dual role for miRNAs in autoimmune demyelination. In particular, the enrichment in miRNAs mediating pro-myelinating signals suggests an active involvement of these non-coding RNAs in the homeostatic response toward neuroinflammatory injury. BioMed Central 2020-10-12 /pmc/articles/PMC7552381/ /pubmed/33046105 http://dx.doi.org/10.1186/s12974-020-01964-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ma, Qin
Matsunaga, Atsuko
Ho, Brenda
Oksenberg, Jorge R.
Didonna, Alessandro
Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis
title Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis
title_full Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis
title_fullStr Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis
title_full_unstemmed Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis
title_short Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis
title_sort oligodendrocyte-specific argonaute profiling identifies micrornas associated with experimental autoimmune encephalomyelitis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552381/
https://www.ncbi.nlm.nih.gov/pubmed/33046105
http://dx.doi.org/10.1186/s12974-020-01964-5
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