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IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation

Regulation of innate immune responses is essential for maintenance of immune homeostasis and development of an appropriate immunity against microbial infection. We show here that miR-3614-5p, product of the TRIM25 host gene, is induced by type I interferon (IFN-I) in several human non-immune and imm...

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Autores principales: Vuillier, Françoise, Li, Zhi, Black, Iain, Cruciani, Melania, Rubino, Erminia, Michel, Frédérique, Pellegrini, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354889/
https://www.ncbi.nlm.nih.gov/pubmed/35935998
http://dx.doi.org/10.3389/fimmu.2022.939907
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author Vuillier, Françoise
Li, Zhi
Black, Iain
Cruciani, Melania
Rubino, Erminia
Michel, Frédérique
Pellegrini, Sandra
author_facet Vuillier, Françoise
Li, Zhi
Black, Iain
Cruciani, Melania
Rubino, Erminia
Michel, Frédérique
Pellegrini, Sandra
author_sort Vuillier, Françoise
collection PubMed
description Regulation of innate immune responses is essential for maintenance of immune homeostasis and development of an appropriate immunity against microbial infection. We show here that miR-3614-5p, product of the TRIM25 host gene, is induced by type I interferon (IFN-I) in several human non-immune and immune cell types, in particular in primary myeloid cells. Studies in HeLa cells showed that miR-3614-5p represses both p110 and p150 ADAR1 and reduces constitutive and IFN-induced A-to-I RNA editing. In line with this, activation of innate sensors and expression of IFN-β and the pro-inflammatory IL-6 are promoted. MiR-3614-5p directly targets ADAR1 transcripts by binding to one specific site in the 3’UTR. Moreover, we could show that endogenous miR-3614-5p is associated with Ago2 and targets ADAR1 in IFN-stimulated cells. Overall, we propose that, by reducing ADAR1, IFN-I-induced miR-3614-5p contributes to lowering the activation threshold of innate sensors. Our findings provide new insights into the role of miR-3614-5p, placing it as a potential fine tuner of dsRNA metabolism, cell homeostasis and innate immunity.
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spelling pubmed-93548892022-08-06 IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation Vuillier, Françoise Li, Zhi Black, Iain Cruciani, Melania Rubino, Erminia Michel, Frédérique Pellegrini, Sandra Front Immunol Immunology Regulation of innate immune responses is essential for maintenance of immune homeostasis and development of an appropriate immunity against microbial infection. We show here that miR-3614-5p, product of the TRIM25 host gene, is induced by type I interferon (IFN-I) in several human non-immune and immune cell types, in particular in primary myeloid cells. Studies in HeLa cells showed that miR-3614-5p represses both p110 and p150 ADAR1 and reduces constitutive and IFN-induced A-to-I RNA editing. In line with this, activation of innate sensors and expression of IFN-β and the pro-inflammatory IL-6 are promoted. MiR-3614-5p directly targets ADAR1 transcripts by binding to one specific site in the 3’UTR. Moreover, we could show that endogenous miR-3614-5p is associated with Ago2 and targets ADAR1 in IFN-stimulated cells. Overall, we propose that, by reducing ADAR1, IFN-I-induced miR-3614-5p contributes to lowering the activation threshold of innate sensors. Our findings provide new insights into the role of miR-3614-5p, placing it as a potential fine tuner of dsRNA metabolism, cell homeostasis and innate immunity. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9354889/ /pubmed/35935998 http://dx.doi.org/10.3389/fimmu.2022.939907 Text en Copyright © 2022 Vuillier, Li, Black, Cruciani, Rubino, Michel and Pellegrini https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Vuillier, Françoise
Li, Zhi
Black, Iain
Cruciani, Melania
Rubino, Erminia
Michel, Frédérique
Pellegrini, Sandra
IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation
title IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation
title_full IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation
title_fullStr IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation
title_full_unstemmed IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation
title_short IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation
title_sort ifn-i inducible mir-3614-5p targets adar1 isoforms and fine tunes innate immune activation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354889/
https://www.ncbi.nlm.nih.gov/pubmed/35935998
http://dx.doi.org/10.3389/fimmu.2022.939907
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