Imperial College London
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Dr John S Tregoning

Faculty of Medicine, Department of Infectious Disease

Professor in Vaccine Immunology
 
 
 
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Contact

 

john.tregoning Website

 
 
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Location

 

456 (Shattock Group)Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Shelkovnikova:2019:10.1016/j.celrep.2019.11.094,
author = {Shelkovnikova, TA and An, H and Skelt, L and Tregoning, JS and Humphreys, IR and Buchman, VL},
doi = {10.1016/j.celrep.2019.11.094},
journal = {Cell Reports},
pages = {4496--4508.E4},
title = {Antiviral immune response as a trigger of FUS proteinopathy in amyotrophic lateral sclerosis},
url = {http://dx.doi.org/10.1016/j.celrep.2019.11.094},
volume = {29},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Mutations in the FUS gene cause familial amyotrophic lateral sclerosis (ALS-FUS). In ALS-FUS, FUS-positive inclusions are detected in the cytoplasm of neurons and glia, a condition known as FUS proteinopathy. Mutant FUS incorporates into stress granules (SGs) and can spontaneously form cytoplasmic RNA granules in cultured cells. However, it is unclear what can trigger the persistence of mutant FUS assemblies and lead to inclusion formation. Using CRISPR/Cas9 cell lines and patient fibroblasts, we find that the viral mimic dsRNA poly(I:C) or a SG-inducing virus causes the sustained presence of mutant FUS assemblies. These assemblies sequester the autophagy receptor optineurin and nucleocytoplasmic transport factors. Furthermore, an integral component of the antiviral immune response, type I interferon, promotes FUS protein accumulation by increasing FUS mRNA stability. Finally, mutant FUS-expressing cells are hypersensitive to dsRNA toxicity. Our data suggest that the antiviral immune response is a plausible second hit for FUS proteinopathy.
AU  - Shelkovnikova,TA
AU  - An,H
AU  - Skelt,L
AU  - Tregoning,JS
AU  - Humphreys,IR
AU  - Buchman,VL
DO  - 10.1016/j.celrep.2019.11.094
EP  - 4508
PY  - 2019///
SN  - 2211-1247
SP  - 4496
TI  - Antiviral immune response as a trigger of FUS proteinopathy in amyotrophic lateral sclerosis
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2019.11.094
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000504335700022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/76251
VL  - 29
ER  -
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