title: Regulation of mitochondrial morphology and cell cycle by microRNA-214 targeting Mitofusin2.
abstract: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the increase in CAG repeats beyond 36 at the exon1 of the gene Huntingtin (HTT). Among the various dysfunctions of biological processes in HD, transcription deregulation due to abnormalities in actions of transcription factors has been considered to be one of the important pathological conditions. In addition, deregulation of microRNA (miRNA) expression has been described in HD. Earlier, expression of microRNA-214 (miR-214) has been shown to increase in HD cell models and target HTT gene; the expression of the later being inversely correlated to that of miR-214. In the present communication, we observed that the expressions of several HTT co-expressed genes are modulated by exogenous expression of miR-214 or by its mutant. Among several HTT co-expressed genes, MFN2 was shown to be the direct target of miR-214. Exogenous expression of miR-214, repressed the expression of MFN2, increased the distribution of fragmented mitochondria and altered the distribution of cells in different phases of cell cycle. In summary, we have shown that increased expression of miR-214 observed in HD cell model could target MFN2, altered mitochondrial morphology and deregulated cell cycle. Inhibition of miR-214 could be a possible target of intervention in HD pathogenesis.
authors: Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF, Bidhan Nagar, Kolkata, 700 064, India.
authors: Sudha
authors: S
authors: Bucha
authors: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhan Nagar, Kolkata, 700 064, India.
authors: Debashis
authors: D
authors: Mukhopadhyay
authors: Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF, Bidhan Nagar, Kolkata, 700 064, India; Biomedical Genomics Centre, PG Polyclinic Building (3rd Floor), 5, Suburbun Hospital Road, Kolkata, 700020, India. Electronic address: nitai_sinp@yahoo.com.
authors: Nitai Pada
authors: NP
authors: Bhattacharyya
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015870:Gene Expression; D053263:Gene Regulatory Networks; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C086055:HTT protein, human; D000071058:Huntingtin Protein; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C488751:Mfn2 protein, mouse
keywords: Cell cycle; Huntingtin; Huntington's disease; MicroRNA-214; Mitochondria; Mitofusin2