ADAR1 restricts LINE-1 retrotransposition

Elisa Orecchini, Margherita Doria, Ambra Antonioni, Silvia Galardi, Silvia Anna Ciafrè, Loredana Frassinelli, Carmine Mancone, Claudia Montaldo, Marco Tripodi, Alessandro Michienzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)155-168
Number of pages14
JournalNucleic Acids Research
Volume45
Issue number1
DOIs
Publication statusPublished - Sep 21 2016

    Fingerprint

Keywords

  • Journal Article

Cite this

Orecchini, E., Doria, M., Antonioni, A., Galardi, S., Ciafrè, S. A., Frassinelli, L., Mancone, C., Montaldo, C., Tripodi, M., & Michienzi, A. (2016). ADAR1 restricts LINE-1 retrotransposition. Nucleic Acids Research, 45(1), 155-168. https://doi.org/10.1093/nar/gkw834