title: ADAR1 restricts LINE-1 retrotransposition.
abstract: Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosines to inosines in double-stranded RNAs. ADAR1 was demonstrated to be functional on different viruses exerting either antiviral or proviral effects. Concerning HIV-1, several studies showed that ADAR1 favors viral replication. The aim of this study was to investigate the composition of the ADAR1 ribonucleoprotein complex during HIV-1 expression. By using a dual-tag affinity purification procedure in cells expressing HIV-1 followed by mass spectrometry analysis, we identified 14 non-ribosomal ADAR1-interacting proteins, most of which are novel. A significant fraction of these proteins were previously demonstrated to be associated to the Long INterspersed Element 1 (LINE1 or L1) ribonucleoparticles and to regulate the life cycle of L1 retrotransposons that continuously re-enter host-genome.Hence, we investigated the function of ADAR1 in the regulation of L1 activity.By using different cell-culture based retrotransposition assays in HeLa cells, we demonstrated a novel function of ADAR1 as suppressor of L1 retrotransposition. Apparently, this inhibitory mechanism does not occur through ADAR1 editing activity. Furthermore, we showed that ADAR1 binds the basal L1 RNP complex. Overall, these data support the role of ADAR1 as regulator of L1 life cycle.
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, Rome 00133, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Orecchini
authors.affiliation: Laboratory of Immunoinfectivology, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, Rome 00165, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Doria
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, Rome 00133, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Antonioni
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, Rome 00133, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galardi
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, Rome 00133, Italy.
authors.forename: Silvia Anna
authors.initials: SA
authors.lastname: Ciafrè
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, Rome 00133, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Frassinelli
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Italy.|L. Spallanzani National Institute for Infectious Diseases, IRCCS, via Portuense 292, Rome 00149, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Mancone
authors.affiliation: L. Spallanzani National Institute for Infectious Diseases, IRCCS, via Portuense 292, Rome 00149, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Montaldo
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Italy.|L. Spallanzani National Institute for Infectious Diseases, IRCCS, via Portuense 292, Rome 00149, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tripodi
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, Rome 00133, Italy alessandro.michienzi@uniroma2.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Michienzi
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism; D001681:Biological Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D058977:Molecular Sequence Annotation; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018626:Retroelements; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D006360:Heat-Shock Proteins; D016601:RNA-Binding Proteins; D018626:Retroelements; D012261:Ribonucleoproteins; C000595356:ADAR protein, human; D000243:Adenosine Deaminase