Wild‐type and mutant SOD1 localizes to RNA‐rich structures in cells and mice but does not bind RNA.

Autor:	Da Ros, Matteo, Deol, Harmeen K., Savard, Alexandre, Guo, Huishan, Meiering, Elizabeth M., Gibbings, Derrick
Předmět:	ALTERNATIVE RNA splicing CELL anatomy RNA RNA-binding proteins GENETIC mutation AMYOTROPHIC lateral sclerosis RNA metabolism RNA splicing
Zdroj:	Journal of Neurochemistry; Feb2021, Vol. 156 Issue 4, p524-538, 15p
Abstrakt:	Many of the genes whose mutation causes Amyotrophic Lateral Sclerosis (ALS) are RNA‐binding proteins which localize to stress granules, while others impact the assembly, stability, and elimination of stress granules. This has led to the hypothesis that alterations in the dynamics of stress granules and RNA biology cause ALS. Genetic mutations in Superoxide Dismutase 1 (SOD1) also cause ALS. Evidence demonstrates that SOD1 harboring ALS‐linked mutations is recruited to stress granules, induces changes in alternative splicing, and could be an RNA‐binding protein. Whether SOD1 inclusions contain RNA in disease models and whether SOD1 directly binds RNA remains uncertain. We applied methods including cross‐linking immunoprecipitation and in vitro gel shift assays to detect binding of SOD1 to RNA in vitro, in cells with and without stress granules, and in mice expressing human SOD1 G93A. We find that SOD1 localizes to RNA‐rich structures including stress granules, and SOD1 inclusions in mice contain mRNA. However, we find no evidence that SOD1 directly binds RNA. This suggests that SOD1 may impact stress granules, alternative splicing and RNA biology without binding directly to RNA. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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