title: Micro RNA -214,-150,-146a and-125b target Huntingtin gene.
abstract: We observed earlier that expressions of several micro RNAs (miRNAs) are altered in a cell model of Huntington's disease (HD). As genes involved in different neurodegenerative diseases are targeted by miRNAs, we searched databases to find out whether Huntingtin gene (HTT), mutation to which causes HD, is a target of any miRNA. Among many miRNAs that are predicted to target HTT, we showed using various experimental approaches that miR-214, miR-150, miR-146a and miR-125b could target both human HTT and mouse Htt. Luciferase reporter vectors containing 3'-UTRs of mouse and human HTT showed reduction in relative luciferase activities on exogenous expression of cloned miRNAs.  Loss of function studies with miRNA inhibitors led to the revival of luciferase activities of cloned 3'-UTR of HTT.  Exogenous expression of these miRNAs reduced the expression of endogenous Htt in mouse cells. Expression of miRNAs with mutations at seed sequences neither reduced the reporter luciferase activities nor the endogenous expression of Htt. Taking together, we showed that miR-214, miR-150, miR-146a and miR-125b targeted HTT. Besides, the exogenous expression of wild type miRNAs reduced HTT aggregates formed by the recombinant exon1 of HTT gene that codes for 83Q tagged with 3'-UTR of Htt, as observed by filter retardation assay and confocal microscopy. In summary, regulation of HTT by miRNAs might provide a new mechanism for the modulation of HD.
authors: Stuctural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India.
authors: Mithun
authors: M
authors: Sinha
authors: Jayeeta
authors: J
authors: Ghose
authors: Nitai P
authors: NP
authors: Bhattarcharyya
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D000071058:Huntingtin Protein; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D000071058:Huntingtin Protein; D008156:Luciferases; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C086055:HTT protein, human; C506812:Htt protein, mouse; C531888:MIRN125 microRNA, human; C542542:MIRN146 microRNA, human; C533097:MIR150, human; C547397:MIRN214 microRNA, human