title: Arsenic programmes cellular genomic-immunity through miR-2909 RNomics.
abstract: It is widely recognized that human cells are equipped with innate antiviral-RNA armour involving the production of type I interferons and APOBEC3G (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G) gene-product. Although arsenic has been shown to have paradoxical effect on one arm of this armour involving APOBEC3G, the exact molecular mechanism of its action in this regard is far from clear. The present study, addressed to explore as to how arsenic programmes this innate antiviral-RNA cellular-sensing pathway, clearly revealed that arsenic programmes this innate cellular antiviral genomic response through its inherent capacity to initiate cellular miR-2909 RNomics pathway, involving not only the modulation of APOBEC3G gene but also KLF4 (Kruppel-like factor 4) dependent regulation of gene coding for IKBKε (Inhibitor of nuclear factor kappa-B kinase subunit epsilon) which in turn modulates RIG-I (retinoic acid-inducible gene 1) pathway responsible for the production of IFNβ (interferon beta) through restriction of CYLD (Cylindromatosis) deubiqutinating activity. This restricted inhibitory enzyme activity of CYLD upon NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) also ensures sustained expression of miR-2909. Our results for the first time show that cellular miR-2909 RNomics may constitute an innate genomic armour to promote as well as restrict retroviral infection.
authors.affiliation: Department of Experimental Medicine & Biotechnology, Post-graduate Institute of Medical Education & Research, Chandigarh 160012, India. Electronic address: dkaul_24@hotmail.com.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaul
authors.affiliation: Department of Experimental Medicine & Biotechnology, Post-graduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Experimental Medicine & Biotechnology, Post-graduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Experimental Medicine & Biotechnology, Post-graduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: M
authors.initials: M
authors.lastname: Arora
authors.affiliation: Department of Experimental Medicine & Biotechnology, Post-graduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Mansi
authors.initials: M
authors.lastname: Arora
mesh_terms: D000071480:APOBEC-3G Deaminase; D000998:Antiviral Agents / Q000493:pharmacokinetics; D001151:Arsenic / Q000494:pharmacology*; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000494:pharmacology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics; D000074749:Deubiquitinating Enzyme CYLD; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics; D007111:Immunity, Cellular / Q000187:drug effects* / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011971:Receptors, Immunologic; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; D016328:NF-kappa B; D011971:Receptors, Immunologic; D025521:Tumor Suppressor Proteins; D016899:Interferon-beta; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D001151:Arsenic
keywords: APOBEC3G; Apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G; Arsenic; As; CYLD; Cylindromatosis; FCS; Foetal Calf Serum; Gene regulation; IFNβ; IKBKε; IRF3; Inhibitor of nuclear factor kappa-B kinase subunit epsilon; Interferon beta; Interferon regulatory factor 3; KLF4; Kruppel-like factor4; MicroRNA; NFκB; Nuclear factor kappa B; PBMCs; Peripheral blood mononuclear cells; RIG1; Retinoic acid-inducible gene 1; Viral-RNA sensing; miR-2909; miRNA