title: Dme-miR-314-3p modulation in Cr(VI) exposed Drosophila affects DNA damage repair by targeting mus309.
abstract: microRNAs (miRNAs) as one of the major epigenetic modulators negatively regulate mRNAs at post transcriptional level. It was therefore hypothesized that modulation of miRNAs by hexavalent Chromium [Cr(VI)], a priority environmental chemical, can affect DNA damage. In a genetically tractable model, Drosophila melanogaster, role of maximally up-regulated miRNA, dme-miR-314-3p, on DNA damage was examined by exposing the third instar larvae to 5.0-20.0 μg/ml Cr(VI) for 24 and 48 h. mus309, a Drosophila homologue of human Bloom's syndrome and predicted as one of the potential targets of this miRNA, was confirmed as its target by 5'RLM-RACE assay. A significant down-regulation of mus309 was observed in dme-miR-314-3p overexpression strain (myo-gal4>UAS-miR-314-3p) as compared with that in parental strains (myo-gal4 and UAS-miR-314-3p) and in w(1118). A significant increase in DNA damage including double strand breaks generation was observed in exposed myo-gal4>UAS-miR-314 and mus309 mutants as compared with that in parental strain and in unexposed control. A significant down-regulation of cell cycle regulation genes (CycA, CycB and cdc2) was observed in these exposed genotypes. Collectively, the study demonstrates that dme-miR-314-3p can mediate the downregulation of repair deficient gene mus309 leading to increased DNA damage and cell cycle arrest in exposed organism which may affect Cr(VI) mediated carcinogenesis.
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific Innovation & Research (AcSIR), CSIR-IITR Campus, Lucknow, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Chandra
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Rehana
authors.initials: R
authors.lastname: Khatoon
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Saini
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific Innovation & Research (AcSIR), CSIR-IITR Campus, Lucknow, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Vimal
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific Innovation & Research (AcSIR), CSIR-IITR Campus, Lucknow, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Singh
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific Innovation & Research (AcSIR), CSIR-IITR Campus, Lucknow, India. Electronic address: dkchowdhuri@iitr.res.in.
authors.forename: D Kar
authors.initials: DK
authors.lastname: Chowdhuri
mesh_terms: D000818:Animals; D002857:Chromium / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004330:Drosophila / Q000235:genetics; D041981:Gastrointestinal Tract / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D053484:RecQ Helicases / Q000235:genetics*
chemical_list: C586149:MIRN314 microRNA, Drosophila; D035683:MicroRNAs; D002857:Chromium; C074702:chromium hexavalent ion; C097151:Bloom syndrome protein; D053484:RecQ Helicases
keywords: Cell cycle; Cr(VI); DNA damage; Drosophila; microRNA