Human Ubiquitin-Specific Peptidase 18 Is Regulated by microRNAs via the 3'Untranslated Region, A Sequence Duplicated in Long Intergenic Non-coding RNA Genes Residing in chr22q11.21

Autor: Rubino, Erminia, Cruciani, Melania, Tchitchek, Nicolas, Le Tortorec, Anna, ROLLAND, Antoine, Veli, Önay, Vallet, Leslie, Gaggi, Giulia, Michel, Frédérique, Dejucq-Rainsford, Nathalie, Pellegrini, Sandra
Přispěvatelé: Signalisation des Cytokines - Cytokine Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie, physiopathologie et thérapeutique (ED 394), Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Research in the Unit of Cytokine Signaling is funded by the Institut Pasteur, the Fondation pour la Recherche Médicale (Equipe FRM DEQ20170336741) and the Institut National de la Santé et de la Recherche Médicale (Inserm). ER was supported by Sorbonne Université and by FRM. MC was supported by the FRM grant above. GG and ÖV were supported by the Erasmus plus programme of the EU commission. Work at Rennes University is funded by Inserm and Défis Scientifiques Emergents., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Gestionnaire, HAL Sorbonne Université 5
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Genetics
Frontiers in Genetics, Frontiers, 2021, 11, ⟨10.3389/fgene.2020.627007⟩
Frontiers in Genetics, 2021, 11, ⟨10.3389/fgene.2020.627007⟩
ISSN: 1664-8021
Popis: International audience; Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of IFN-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here, we identified microRNAs (miRNAs) that efficiently target USP18 through binding to the 3’untranslated region (3’UTR). Among these, three miRNAs are particularly enriched in circulating monocytes which exhibit low baseline USP18. Intriguingly, the USP18 3’UTR sequence is duplicated in human and chimpanzee genomes. In humans, four USP18 3’UTR copies were previously found to be embedded in long intergenic non-coding (linc) RNA genes residing in chr22q11.21 and known as FAM247A-D. Here, we further characterized their sequence and measured their expression profile in human tissues. Importantly, we describe an additional lincRNA bearing USP18 3’UTR (here linc-UR-B1) that is expressed only in testis. RNA-seq data analyses from testicular cell subsets revealed a positive correlation between linc-UR-B1 and USP18 expression in spermatocytes and spermatids. Overall, our findings uncover a set of miRNAs and lincRNAs, which may be part of a network evolved to fine-tune baseline USP18, particularly in cell types where IFN responsiveness needs to be tightly controlled.
Databáze: OpenAIRE
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