The FUS protein: Physiological functions and a role in amyotrophic lateral sclerosis

Efimova, A. D.; Овчинников, Р. К.; Roman, Andrei; Maltsev, Andrey V.; Grigoriev, V. V.; Ковражкина, Е. А.; Skvortsova, Veronica I.

doi:10.1134/s0026893317020091

Cited by 20 publications

(21 citation statements)

References 103 publications

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“…Fused in sarcoma (FUS) is an RNA-binding protein that is mainly localised in the nucleus and plays a crucial role in RNA transcription. It also plays a role in DNA repair regulation, transcription, splicing, RNA transport and local translation [8]. The overexpression of FUS promotes malignant progression of non-small cell lung cancer [9] and cervical cancer [10].…”

Section: Introductionmentioning

confidence: 99%

Interaction of BACH2 with FUS promotes malignant progression of glioma cells via the TSLNC8–miR‐10b‐5p–WWC3 pathway

et al. 2020

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Glioma, a common malignant tumour of the human central nervous system, has poor prognosis and limited treatment options. Dissecting the biological mechanisms underlying glioma pathogenesis can facilitate the development of better therapies. Here, we investigated the endogenous expression of BTB and CNC homolog 2 (BACH2), fused in sarcoma (FUS), TSLNC8 and microRNA (miR)-10b-5p in glioma cells and tissues. We studied the interaction between BACH2 and FUS and its contribution to glioma progression. We demonstrated that the interaction between BACH2 and FUS promoted glioma progression via transcriptional inhibition of TSLNC8. Overexpression of TSLNC8 restrained glioma progression by suppressing miR-10b-5p. Binding of TSLNC8 to miR-10b-5p attenuated the suppression of WWC family member 3 (WWC3) by miR-10b-5p and activated the Hippo signalling pathway. Growth of subcutaneous xenografts could be inhibited by knockdown of BACH2 or FUS, by overexpressing TSLNC8 or a combination of the three, also leading to a prolonged survival in nude mice. Our results indicate that the BACH2 and FUS/TSLNC8/miR-10b-5p/WWC3 axis is responsible for glioma development and could serve as a potential target for the development of new glioma therapies.

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Section: Introductionmentioning

confidence: 99%

Interaction of BACH2 with FUS promotes malignant progression of glioma cells via the TSLNC8–miR‐10b‐5p–WWC3 pathway

et al. 2020

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“…Interestingly, zinc ions were found to play a critical role in the development of several different NDs including AD and PD. Zinc can bind not only to a number of prone-toaggregate proteins implicated in neurodegeneration (such as amyloid-β [17], FUS/TLS [18], α-synuclein [19], TDP-43 [20,21], etc.) and favor their aggregation, but also induce aggregation of stable proteins [22].…”

Section: Introductionmentioning

confidence: 99%

Zinc Induces Temperature-Dependent Reversible Self-Assembly of Tau

Roman

Devred

Byrne

et al. 2019

Journal of Molecular Biology

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Tau is an intrinsically disordered microtubule-associated protein that is implicated in several neurodegenerative disorders called tauopathies. In these diseases, Tau is found in the form of intracellular inclusions that consist of aggregated paired helical filaments (PHFs) in neurons. Given the importance of this irreversible PHF formation in neurodegenerative disease, Tau aggregation has been extensively studied. Several different factors, such as mutations or post translational modifications, have been shown to influence the formation of late-stage non-reversible Tau aggregates. It was recently shown that zinc ions accelerated heparin-induced oligomerization of Tau constructs. Indeed, in vitro studies of PHFs have usually been performed in the presence of additional co-factors, such as heparin, in order to accelerate their formation. Using turbidimetry, we investigated the impact of zinc ions on Tau in the absence of heparin and found that zinc is able to induce a temperature-dependent reversible oligomerization of Tau. The obtained oligomers were not amyloid-like and dissociated instantly following zinc chelation or a temperature decrease. Finally, a combination of isothermal titration calorimetry and dynamic light scattering experiments showed zinc binding to a high-affinity binding site and three low-affinity sites on Tau, accompanied by a change in Tau folding. Altogether, our findings stress the importance of zinc in Tau oligomerization. This newly identified Zn-induced oligomerization mechanism may be a part of a pathway different of and concurrent to Tau aggregation cascade leading to PHF formation.

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“…FUS can shuttle between the nucleus and cytoplasm, and is detected at the pre-synaptic site of hippocampal neurons and at the neuromuscular junction (NMJ) (Schoen et al, 2015;So et al, 2018). FUS plays various cellular functions including transcriptional activation, RNA splicing, mRNA trafficking and translation, and DNA repair as well as genome stability by direct binding to nucleic acid molecules (Efimova et al, 2017). It has been shown that FUS can act on mRNA trafficking and local translation in neurons.…”

Section: Fused In Sarcoma/translocated In Liposarcoma (Fus) For Localmentioning

confidence: 99%

The Role of RNA Binding Proteins for Local mRNA Translation: Implications in Neurological Disorders

Thelen

Kye

2020

Front. Mol. Biosci.

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As neurons are one of the most highly polarized cells in our body, they require sophisticated cellular mechanisms to maintain protein homeostasis in their subcellular compartments such as axons and dendrites. When neuronal protein homeostasis is disturbed due to genetic mutations or deletions, this often results in degeneration of neurons leading to devastating outcome such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and fragile X syndrome (FXS). Ribonucleoprotein (RNP) complexes are macromolecular complexes composed of RNA binding proteins (RBPs) and their target RNAs. RBPs contain RNA binding domains and bind to RNA molecules via specific sequence motifs. RNP complexes have various functions in gene expression including messenger RNA (mRNA) trafficking, RNA processing and silencing. In neurons, RBPs deliver specific sets of mRNAs to subcellular compartments such as axons and dendrites to be locally translated. Mutations or deletions in genes coding for RNPs have been reported as causes for neurological disorders such as SMA, ALS, and FXS. As RBPs determine axonal or dendritic mRNA repertoires as well as proteomes by trafficking selective mRNAs and regulating local protein synthesis, they play a crucial role for neuronal function. In this review, we summarize the role of well-known RBPs, SMN, TDP-43, FUS, and FMRP, and review their function for local protein synthesis in neurons. Furthermore, we discuss their pathological contribution to the neurological disorders.

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The FUS protein: Physiological functions and a role in amyotrophic lateral sclerosis

Cited by 20 publications

References 103 publications

Interaction of BACH2 with FUS promotes malignant progression of glioma cells via the TSLNC8–miR‐10b‐5p–WWC3 pathway

Interaction of BACH2 with FUS promotes malignant progression of glioma cells via the TSLNC8–miR‐10b‐5p–WWC3 pathway

Zinc Induces Temperature-Dependent Reversible Self-Assembly of Tau

The Role of RNA Binding Proteins for Local mRNA Translation: Implications in Neurological Disorders

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