Neuronal tissue-specific ribonucleoprotein complex formation on SOD1 mRNA: Alterations by ALS SOD1 mutations

Neurobiology of Disease

Wendy Strong¹  Wei-wen Ge¹  Cheryl Leystra-Lantz¹  Jesse McLean¹  Teresa R. Sanelli¹  Weiyan Wen¹  Michael J. Strong¹ 

[1] Cell Biology Research Group, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada N6A;

关键词: Amyotrophic lateral sclerosis (ALS);    Copper/Zinc superoxide dismutase (SOD1);    Ribonucleoprotein complex;    Mutations;    Tissue specificity;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown