RRC ID 57232
著者 Lo Piccolo L, Jantrapirom S, Nagai Y, Yamaguchi M.
タイトル FUS toxicity is rescued by the modulation of lncRNA hsrω expression in Drosophila melanogaster.
ジャーナル Sci Rep
Abstract FUS is an aggregation-prone hnRNP involved in transcriptional and post-transcriptional regulation that aberrantly forms immunoreactive inclusion bodies in a range of neurological diseases classified as FUS-proteinopathies. Although FUS has been extensively examined, the underlying molecular mechanisms of these diseases have not yet been elucidated in detail. We previously reported that RNAi of the lncRNA hsrω altered the expression and sub-cellular localization of Drosophila FUS in the central nervous system of the fly. In order to obtain a clearer understanding of the role of hsrω in FUS toxicity, we herein drove the expression of human FUS in Drosophila eyes with and without a hsrω RNAi background. We found that hFUS was largely soluble and also able to form aggregates. As such, hFUS was toxic, inducing an aberrant eye morphology with the loss of pigmentation. The co-expression of hsrω double-stranded RNA reduced hFUS transcript levels and induced the formation of cytoplasmic non-toxic hFUS-LAMP1-insoluble inclusions. The combination of these events caused the titration of hFUS molar excess and a removal of hFUS aggregates to rescue toxicity. These results revealed the presence of a lncRNA-dependent pathway involved in the management of aggregation-prone hnRNPs, suggesting that properly formed FUS inclusions are not toxic to cells.
巻・号 7(1)
ページ 15660
公開日 2017-11-15
DOI 10.1038/s41598-017-15944-y
PII 10.1038/s41598-017-15944-y
PMID 29142303
PMC PMC5688078
MeSH Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / growth & development Central Nervous System / growth & development Central Nervous System / metabolism Drosophila melanogaster / genetics Eye / growth & development Eye / metabolism Gene Expression Regulation / genetics Heterogeneous-Nuclear Ribonucleoproteins / genetics Lysosomal-Associated Membrane Protein 1 / genetics Pigmentation / genetics* Protein Aggregates / genetics* RNA, Double-Stranded / genetics RNA, Long Noncoding / genetics* RNA-Binding Protein FUS / genetics*
IF 4.011
引用数 6
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