C9ORF72 GGGGCC repeat-associated non-AUG translation is upregulated by stress through eIF2α phosphorylation

Weiwei Cheng; Shaopeng Wang; Alexander A. Mestre; Chenglai Fu; Andres Makarem; Fengfan Xian; Lindsey R. Hayes; Rodrigo Lopez-Gonzalez; Kevin Drenner; Jie Jiang; Don W. Cleveland; Shuying Sun

doi:10.1038/s41467-017-02495-z

Nature Communications (Jan 2018)

C9ORF72 GGGGCC repeat-associated non-AUG translation is upregulated by stress through eIF2α phosphorylation

Weiwei Cheng,
Shaopeng Wang,
Alexander A. Mestre,
Chenglai Fu,
Andres Makarem,
Fengfan Xian,
Lindsey R. Hayes,
Rodrigo Lopez-Gonzalez,
Kevin Drenner,
Jie Jiang,
Don W. Cleveland,
Shuying Sun

Affiliations

Weiwei Cheng: Department of Pathology and Brain Science Institute, Johns Hopkins University School of Medicine
Shaopeng Wang: Department of Pathology and Brain Science Institute, Johns Hopkins University School of Medicine
Alexander A. Mestre: Department of Pathology and Brain Science Institute, Johns Hopkins University School of Medicine
Chenglai Fu: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine
Andres Makarem: Department of Pathology and Brain Science Institute, Johns Hopkins University School of Medicine
Fengfan Xian: Department of Pathology and Brain Science Institute, Johns Hopkins University School of Medicine
Lindsey R. Hayes: Brain Science Institute and Department of Neurology, Johns Hopkins University School of Medicine
Rodrigo Lopez-Gonzalez: Department of Neurology, University of Massachusetts Medical School
Kevin Drenner: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego
Jie Jiang: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego
Don W. Cleveland: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego
Shuying Sun: Department of Pathology and Brain Science Institute, Johns Hopkins University School of Medicine

DOI: https://doi.org/10.1038/s41467-017-02495-z
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 12

Abstract

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Hexanucleotide GGGGCC repeat expansion in C9ORF72 is the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here the authors show that (GGGGCC) n translation can initiate without a 5′-cap, and this cap-independent translation is upregulated by stress mediated through eIF2α phosphorylation.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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