title: Neuronal tissue-specific ribonucleoprotein complex formation on SOD1 mRNA: alterations by ALS SOD1 mutations.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal disease of unknown etiology. Mutations in copper/zinc superoxide dismutase (SOD1) are the most commonly associated genetic abnormality. Given that SOD1 is ubiquitously expressed, the exclusive vulnerability of motor neurons is one of the most puzzling issues in ALS research. We here report that wild-type SOD1 mRNA forms ribonucleoprotein (RNP) complexes with protein homogenates of neuronal tissue but not with homogenates of non-neuronal tissues. 3' Untranslated region of SOD1 mRNA-dependent RNP complexes functioned to stabilize SOD1 mRNA. Moreover, SOD1 mRNAs harboring ALS-associated mutations, including silent mutations, were deficient in forming RNP complexes. In contrast, SOD1 mRNAs harboring artificial mutations, not known to be associated with ALS, demonstrated preserved RNP complex formation. This paper reports RNP complex formation on SOD1 mRNA as a neuronal tissue-specific and ALS-associated mutation sensitive feature.
authors.affiliation: Cell Biology Research Group, Robarts Research Institute, London, Ontario, Canada.
authors.forename: Wei-wen
authors.initials: WW
authors.lastname: Ge
authors.forename: Cheryl
authors.initials: C
authors.lastname: Leystra-Lantz
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Sanelli
authors.forename: Jesse
authors.initials: J
authors.lastname: McLean
authors.forename: Weiyan
authors.initials: W
authors.lastname: Wen
authors.forename: Wendy
authors.initials: W
authors.lastname: Strong
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Strong
mesh_terms: D006801:Humans; D016472:Motor Neuron Disease / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D009474:Neurons; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014158:Transcription, Genetic
chemical_list: D015347:RNA Probes; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C000606290:SOD1 protein, human; D012313:RNA; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1