Pur-alpha is a DNA and RNA-binding protein was recently shown to bind C9ORF72 repeat expansions and potentially contribute to the pathogenesis of ALS (Xu et. al., 2013, Sareen et. al., 2013). In a paper published Jan 4 in Acta Neuropathologica online, researchers from Louisiana State University and University of Pittsburgh report that Pur-alpha is also an important player in ALS caused by mutations in fused in sarcoma (FUS). In lyphoblastoid cells from ALS patients harboring FUS mutations, Pur-alpha colocalized with mutant FUS in cytoplasmic stress granules (SG) after a stress insult. Pur-alpha is necessary for SG formation, since its suppression via shRNA in human cell lines prevented the SGs from forming. In primary motor neurons, overexpression of Pur-alpha was sufficient to restore nuclear localization to mutant FUS and alleviate FUS toxicity. These findings, together with an earlier report (Di Salvio et. al. 2015), point to Pur-alpha as a regulator of stress granule dynamics and potential therapeutic target in ALS.
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Daigle JG, Krishnamurthy K, Ramesh N, Casci I, Monaghan J, McAvoy K, Godfrey EW, Daniel DC, Johnson EM, Monahan Z, Shewmaker F, Pasinelli P, Pandey UB. Pur-alpha regulates cytoplasmic stress granule dynamics and ameliorates FUS toxicity. Acta Neuropathol. 2016 Jan 4. [Pubmed].
Di Salvio M, Piccinni V, Gerbino V, Mantoni F, Camerini S, Lenzi J, Rosa A, Chellini L, Loreni F, Carrì MT, Bozzoni I, Cozzolino M, Cestra G. Pur-alpha functionally interacts with FUS carrying ALS-associated mutations. Cell Death Dis. 2015 Oct 22;6:e1943. [Pubmed].