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

Abstract : 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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Contributor : Françoise Vuillier Connect in order to contact the contributor
Submitted on : Tuesday, August 30, 2022 - 4:00:44 PM
Last modification on : Thursday, September 1, 2022 - 3:45:32 AM


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Françoise Vuillier, Zhi Li, Iain Black, Melania Cruciani, Erminia Rubino, et al.. IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation. Frontiers in Immunology, Frontiers, 2022, 13, pp.939907. ⟨10.3389/fimmu.2022.939907⟩. ⟨pasteur-03764857⟩



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