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: Swati Chandra, Rehana Khatoon, Ashutosh Pandey, Sanjay Saini, Divya Vimal, Pallavi Singh, D Kar Chowdhuri
• Journal: Journal of hazardous materials (J Hazard Mater) Vol. 304 Pg. 360-9 (Mar 05 2016) ISSN: 1873-3336 [Electronic] Netherlands
• PMID: 26590872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• MIRN314 microRNA, Drosophila
• MicroRNAs
• Chromium
• chromium hexavalent ion
• Bloom syndrome protein
• RecQ Helicases

Topics

• Animals
• Chromium (toxicity)
• DNA Damage
• DNA Repair
• Drosophila (genetics)
• Gastrointestinal Tract (metabolism)
• MicroRNAs (genetics)
• RecQ Helicases (genetics)