Dataset Information

FUS toxicity is rescued by the modulation of lncRNA hsr? expression in Drosophila melanogaster.

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 hsr? 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 hsr? in FUS toxicity, we herein drove the expression of human FUS in Drosophila eyes with and without a hsr? 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 hsr? 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.

SUBMITTER: Lo Piccolo L

PROVIDER: S-EPMC5688078 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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FUS toxicity is rescued by the modulation of lncRNA hsrω expression in Drosophila melanogaster.

Lo Piccolo Luca L Jantrapirom Salinee S Nagai Yoshitaka Y Yamaguchi Masamitsu M

Scientific reports 20171115 1

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 n ...[more]

PMID: 29142303

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Dataset Information

FUS toxicity is rescued by the modulation of lncRNA hsr? expression in Drosophila melanogaster.

Publications

FUS toxicity is rescued by the modulation of lncRNA hsrω expression in Drosophila melanogaster.

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