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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis
Human Molecular Genetics, Volume 24, No. 5, Year 2015
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Description
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of motor neurons. Causative mutations in the global RNA-processing proteins TDP-43 and FUS among others, as well as their aggregation in ALS patients, have identified defects in RNA metabolism as an important feature in this disease. Lethal congenital contracture syndrome 1 and lethal arthrogryposis with anterior horn cell disease are autosomal recessive fetal motor neuron diseases that are caused by mutations in another global RNA-processing protein, hGle1. In this study,we carried out the first screening of GLE1 in ALS patients (173 familial and 760 sporadic) and identified 2 deleterious mutations (1 splice site and 1 nonsense mutation) and 1 missense mutation. Functional analysis of the deleterious mutants revealed them to be unable to rescue motor neuron pathology in zebrafish morphants lacking Gle1. Furthermore, in HeLa cells, both mutations caused a depletion of hGle1 at the nuclear pore where it carries out an essential role in nuclear export of mRNA. These results suggest a haploinsufficiency mechanism and point to a causative role for GLE1 mutations in ALS patients. This further supports the involvement of global defects in RNA metabolism in ALS. © The Author 2014.
Authors & Co-Authors
Leblond, Claire S.
Canada, Montreal
Université Mcgill
Girard, Simon L.
Canada, Montreal
University of Montreal
Daoud, Hussein
Canada, Montreal
University of Montreal
Noreau, Anne
Canada, Montreal
University of Montreal
Rochefort, Daniel L.
Canada, Montreal
Université Mcgill
Szuto, Anna
Canada, Montreal
University of Montreal
Camu, William
Unknown Affiliation
Bouchard, Jean Pierre
Canada, Quebec
Université Laval
Dupré, Nicolas
Canada, Quebec
Université Laval
Rouleau, Guy Armand
Canada, Montreal
Université Mcgill
Dion, Patrick A.
Canada, Montreal
Université Mcgill
Canada, Montreal
University of Montreal
Statistics
Citations: 124
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1093/hmg/ddu545
ISSN:
09646906
Research Areas
Cancer