The mRNA translation initiation factor eIF4G1 controls mitochondrial oxidative phosphorylation, axonal morphogenesis, and memory
-
Published:2023-06-12
Issue:25
Volume:120
Page:
-
ISSN:0027-8424
-
Container-title:Proceedings of the National Academy of Sciences
-
language:en
-
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.
Author:
Kim Sung-Hoon12,
Choi Jung-Hyun12,
Marsal-García Laura12ORCID,
Amiri Mehdi12,
Yanagiya Akiko12,
Sonenberg Nahum12ORCID
Affiliation:
1. Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada
2. Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada
Abstract
mRNA translation initiation plays a critical role in learning and memory. The eIF4F complex, composed of the cap-binding protein eIF4E, ATP-dependent RNA helicase eIF4A, and scaffolding protein eIF4G, is a pivotal factor in the mRNA translation initiation process. eIF4G1, the major paralogue of the three eIF4G family members, is indispensable for development, but its function in learning and memory is unknown. To study the role of eIF4G1 in cognition, we used an eIF4G1 haploinsufficient (eIF4G1-1D) mouse model. The axonal arborization of eIF4G1-1D primary hippocampal neurons was significantly disrupted, and the mice displayed impairment in hippocampus-dependent learning and memory. Translatome analysis showed that the translation of mRNAs encoding proteins of the mitochondrial oxidative phosphorylation (OXPHOS) system was decreased in the eIF4G1-1D brain, and OXPHOS was decreased in eIF4G1-silenced cells. Thus, eIF4G1-mediated mRNA translation is crucial for optimal cognitive function, which is dependent on OXPHOS and neuronal morphogenesis.
Funder
Gouvernement du Canada | Canadian Institutes of Health Research
National Research Foundation of Korea
Ministry of Education, Culture, Sports, Science and Technology
Publisher
Proceedings of the National Academy of Sciences
Subject
Multidisciplinary
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献