title: Mutant copper-zinc superoxide dismutase binds to and destabilizes human low molecular weight neurofilament mRNA.
abstract: The mechanism by which mutated copper-zinc superoxide dismutase (SOD1) causes familial amyotrophic lateral sclerosis is believed to involve an adverse gain of function, independent of the physiological antioxidant enzymatic properties of SOD1. In this study, we have observed that mutant SOD1 (G41S, G85A, and G93A) but not the wild type significantly reduced the stability of the low molecular weight neurofilament mRNA in a dosage-dependent manner. We have also demonstrated that mutant SOD1 but not the wild type bound directly to the neurofilament mRNA 3'-untranslated region and that the binding was necessary to induce mRNA destabilization. These observations provide an explanation for a novel gain of function in which mutant SOD1 expression in motor neurons alters an intermediate filament protein expression.
authors.affiliation: Cell Biology Research Group, Robarts Research Institute, London, Ontario N6A 5K8, Canada.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Ge
authors.forename: Weiyan
authors.initials: W
authors.lastname: Wen
authors.forename: Wendy
authors.initials: W
authors.lastname: Strong
authors.forename: Cheryl
authors.initials: C
authors.lastname: Leystra-Lantz
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Strong
mesh_terms: D002460:Cell Line; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D016900:Neurofilament Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D016900:Neurofilament Proteins; D012333:RNA, Messenger; C000606290:SOD1 protein, human; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1