RRM adjacent TARDBP mutations disrupt RNA binding and enhance TDP-43 proteinopathy-Reference-Cited by-同舟云学术

RRM adjacent TARDBP mutations disrupt RNA binding and enhance TDP-43 proteinopathy

Published:2019-10-11 Issue:12 Volume:142 Page:3753-3770
ISSN:0006-8950
Container-title:Brain
language:en
Short-container-title:

Author:

Chen Han-Jou¹²^ORCID,Topp Simon D¹,Hui Ho Sang¹,Zacco Elsa¹,Katarya Malvika¹,McLoughlin Conor¹,King Andrew³,Smith Bradley N¹,Troakes Claire³,Pastore Annalisa¹,Shaw Christopher E¹⁴

Affiliation:

1. United Kingdom Dementia Research Institute Centre, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 125 Coldharbour Lane, Camberwell, SE5 9NU, London, UK

2. York Biomedical Research Institute, Department of Biology, University of York, Wentworth Way, YO10 5DD, York, UK

3. MRC London Neurodegenerative Diseases Brain Bank, De Crespigny Park, SE5 8AF, London, UK

4. Centre for Brain Research, University of Auckland, Auckland, New Zealand

Abstract

TDP-43 is a DNA/RNA binding protein, but whether its interactions with RNA are relevant to inclusion formation in ALS is unclear. Chen et al. report that mutated forms of TDP-43 that are unable to bind RNA have an increased tendency to aggregate, and can mediate toxicity by sequestering wild-type TDP-43.

Funder

Medical Research Council

Wellcome Trust

Motor Neurone Disease Association

UK Dementia Research Institute

Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK

MRC Biomedical NMR Centre

Cancer Research UK

UK Medical Research Council

National Institute for Health Research

NIHR

Dementia Biomedical Research Unit at South London