The RNA-binding protein FUS/TLS is a common aggregate-interacting protein in polyglutamine diseases

Doi, Hiroshi; Koyano, Shigeru; Suzuki, Yume; Nukina, Nobuyuki; Kuroiwa, Yoshihiro

doi:10.1016/j.neures.2009.10.004

Cited by 112 publications

(89 citation statements)

References 10 publications

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“…Moreover, FUS aggregates have been reported in several polyglutamine disorders, including Huntington disease and the spinocerebellar ataxias. 124,125 Because both WT and mutant FUS likely play prominent roles in neurodegeneration, it will be important to define the mechanisms of FUS aggregation.…”

Section: Defining Domains Of Fus Necessary and Sufficient For Aggregamentioning

confidence: 99%

RNA-binding proteins with prion-like domains in ALS and FTLD-U

Gitler

Shorter

2011

Prion

144

121

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and FUS aggregation and toxicity, and to identify genetic modifiers relevant to human disease. We have identified prion-like domains in FUS and TDP-43 and provide evidence that these domains are required for aggregation. Our studies have defined key similarities as well as important differences between the two proteins. Collectively, our findings lead us to suggest that FUS and TDP-43, though similar RNA-binding proteins, likely aggregate and confer disease phenotypes via distinct mechanisms.

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Section: Defining Domains Of Fus Necessary and Sufficient For Aggregamentioning

confidence: 99%

RNA-binding proteins with prion-like domains in ALS and FTLD-U

Gitler

Shorter

2011

Prion

144

121

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“…Actually, before the identification of FUS as a cause of fALS, FUS was first characterized as a protein recruited into the neuronal intranuclear inclusions in HD (Doi et al 2008); furthermore, EWSR1 and TAF15 were also identified as components of insoluble aggregates formed in a HD model mouse expressing Huntingtin with an abnormally expanded polyQ (Doi et al 2008). Later, recruitment of FUS into neuronal intranuclear inclusions has been confirmed also in the other polyQ diseases, SCA 1, 2, 3, and DRPLA (Doi et al 2010;Woulfe et al 2010). In contrast, FUS pathologies were not observed in FTLD with TDP-43 pathologies, multiple system atrophy, fragile X-associated tremor/ataxia syndrome, oculopharyngeal muscular dystrophy, and dementia with Lewy bodies (Doi et al 2010;Woulfe et al 2010).…”

Section: Pathological Inclusions Containing Fet Proteins In Als Casesmentioning

confidence: 97%

Aggregation of FET Proteins as a Pathological Change in Amyotrophic Lateral Sclerosis

Furukawa

Tokuda

2016

Advances in Experimental Medicine and Biology

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Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is characterized by the formation of abnormal inclusions in neurons. While the pathomechanism of ALS remains obscure, a number of proteins have been identified in the inclusion bodies, and the pathological roles of RNA-binding proteins have been increasingly emphasized. Among those, the FET proteins (FUS, EWSR1, TAF15) were recently identified as RNA-binding proteins in pathological inclusions of ALS and other neurodegenerative diseases; moreover, mutations in the genes encoding the FET proteins were found to be associated with familial forms of ALS. FET proteins are normally localized in the nucleus, but the introduction of pathogenic mutations in FET proteins leads to their abnormal redistribution to the cytoplasm, where they form aggregates. While further investigation will be required to understand the intracellular factors controlling the aggregation propensities of FET proteins, they are thought to lose their physiological functions and become toxic through their misfolding/aggregation. Here, we will briefly review recent advances of our understanding of the physiological functions and aggregation behavior of FET proteins in vivo as well as in vitro.

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“…Mutations in the FUS-encoding gene lead to the formation of FUS inclusions in amyotrophic lateral sclerosis 131 and are also observed in diseases caused by the expansion of glutamine-encoding repeats in other proteins. 132 Whether these inclusions are related to amyloidogenesis in vivo is still unclear, 133 although FUS is c apable of forming amyloid-like polymers in vitro. 108 One of interesting hypotheses for both TDP-43-and FUS-associated amyotrophic lateral sclerosis proposes that stress granules are the nucleation sites for the pathologic aggregation of these proteins.…”

Section: Prions Amyloids and Mrna Turnovermentioning

confidence: 99%

Prions, amyloids, and RNA: Pieces of a puzzle

Nizhnikov

Antonets

Bondarev

et al. 2016

Prion

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ABSTRACT. Amyloids are protein aggregates consisting of fibrils rich in b-sheets. Growth of amyloid fibrils occurs by the addition of protein molecules to the tip of an aggregate with a concurrent change of a conformation. Thus, amyloids are self-propagating protein conformations. In certain cases these conformations are transmissible / infectious; they are known as prions. Initially, amyloids were discovered as pathological extracellular deposits occurring in different tissues and organs. To date, amyloids and prions have been associated with over 30 incurable diseases in humans and animals. However, a number of recent studies demonstrate that amyloids are also functionally involved in a variety of biological processes, from biofilm formation by bacteria, to long-term memory in animals. Interestingly, amyloid-forming proteins are highly overrepresented among cellular factors engaged in all stages of mRNA life cycle: from transcription and translation, to storage and degradation. Here we review rapidly accumulating data on functional and pathogenic amyloids associated with mRNA processing, and discuss possible significance of prion and amyloid networks in the modulation of key cellular functions.

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The RNA-binding protein FUS/TLS is a common aggregate-interacting protein in polyglutamine diseases

Cited by 112 publications

References 10 publications

RNA-binding proteins with prion-like domains in ALS and FTLD-U

RNA-binding proteins with prion-like domains in ALS and FTLD-U

Aggregation of FET Proteins as a Pathological Change in Amyotrophic Lateral Sclerosis

Prions, amyloids, and RNA: Pieces of a puzzle

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