title: Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication.
abstract: Small ubiquitin-related modifier (SUMO) protein conjugation onto target proteins regulates multiple cellular functions, including defence against pathogens, stemness and senescence. SUMO1 peptides are limiting in quantity and are thus mainly conjugated to high-affinity targets. Conjugation of SUMO2/3 paralogues is primarily stress inducible and may initiate target degradation. Here we demonstrate that the expression of SUMO1/2/3 is dramatically enhanced by interferons through an miRNA-based mechanism involving the Lin28/let-7 axis, a master regulator of stemness. Normal haematopoietic progenitors indeed display much higher SUMO contents than their differentiated progeny. Critically, SUMOs contribute to the antiviral effects of interferons against HSV1 or HIV. Promyelocytic leukemia (PML) nuclear bodies are interferon-induced domains, which facilitate sumoylation of a subset of targets. Our findings thus identify an integrated interferon-responsive PML/SUMO pathway that impedes viral replication by enhancing SUMO conjugation and possibly also modifying the repertoire of targets. Interferon-enhanced post-translational modifications may be essential for senescence or stem cell self-renewal, and initiate SUMO-dependent proteolysis.
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Umut
authors.initials: U
authors.lastname: Sahin
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Ferhi
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Carnec
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [4] Department CASER, Conservatoire National des Arts et Métiers, Paris 75003, France.
authors.forename: Alessia
authors.initials: A
authors.lastname: Zamborlini
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peres
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Jollivet
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Vitaliano-Prunier
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [4].
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [2] INSERM U944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France [3] CNRS UMR 7212, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lallemand-Breitenbach
mesh_terms: D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D025842:SUMO-1 Protein / Q000235:genetics / Q000276:immunology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000276:immunology*; D014452:Ubiquitins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; C487931:mirnlet7 microRNA, human; D007372:Interferons