김성훈 (McGill University, 현 Stony Brook University) | 한빛사논문 > 한빛사

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김성훈Sunghoon Kim

McGill University, 현 Stony Brook University

CV File 224 kb

Proc. Natl. Acad. Sci. USA, 2023 Jun 20;120(25):e2300008120 | https://doi.org/10.1073/pnas.2300008120 The mRNA translation initiation factor eIF4G1 controls mitochondrial oxidative phosphorylation, axonal morphogenesis, and memory

Sung-Hoon Kim ^a,b,1,Jung-Hyun Choi ^a,b, Laura Marsal-García ^a,b, Mehdi Amiri ^a,b, Akiko Yanagiya ^a,b, and Nahum Sonenberg ^a,b,2

^aRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada
^bDepartment of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada

¹Present address: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794
²Corresponding author: correspondence to Nahum Sonenberg

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.

논문정보

형식Research article
게재일2023년 06월 (BRIC 등록일 2023-06-14)
연구진국외 연구진
분야 생명과학 > 생화학

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