최정현 (McGill University)

한빛사논문

조회204

McGill University

CV File 270 kb

Sci. Adv., Jul 19 2024, 10 (29) | https://doi.org/10.1126/sciadv.adl5638 Repression of mRNA translation initiation by GIGYF1 via disrupting the eIF3-eIF4G1 interaction

Jung-Hyun Choi ^1,2†, Jun Luo ^1,2†, Geoffrey G. Hesketh ³, Shuyue Guo ^1,2, Angelos Pistofidis ², Reese Jalal Ladak ^1,2, Yuxin An ^1,2, Parisa Naeli ⁴, Tommy Alain ⁵, T Martin Schmeing², Anne-Claude Gingras ^6,7, Thomas Duchaine ^1,2, Xu Zhang^1,2*, Nahum Sonenberg ^1,2*, Seyed Mehdi Jafarnejad ^4*

¹Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada.

²Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada.

³Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, NS, Canada.

⁴Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK.

⁵Department of Biochemistry, Microbiology and Immunology, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.

⁶Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada.

⁷Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada.

^*Corresponding authors: X.Z., N.S., S.M.J.

^†These authors contributed equally to this work.

Abstract

Viruses can selectively repress the translation of mRNAs involved in the antiviral response. RNA viruses exploit the Grb10-interacting GYF (glycine-tyrosine-phenylalanine) proteins 2 (GIGYF2) and eukaryotic translation initiation factor 4E (eIF4E) homologous protein 4EHP to selectively repress the translation of transcripts such as Ifnb1, which encodes the antiviral cytokine interferon-β (IFN-β). Herein, we reveal that GIGYF1, a paralog of GIGYF2, robustly represses cellular mRNA translation through a distinct 4EHP-independent mechanism. Upon recruitment to a target mRNA, GIGYF1 binds to subunits of eukaryotic translation initiation factor 3 (eIF3) at the eIF3-eIF4G1 interaction interface. This interaction disrupts the eIF3 binding to eIF4G1, resulting in transcript-specific translational repression. Depletion of GIGYF1 induces a robust immune response by derepressing IFN-β production. Our study highlights a unique mechanism of translational regulation by GIGYF1 that involves sequestering eIF3 and abrogating its binding to eIF4G1. This mechanism has profound implications for the host response to viral infections.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-21)
연구진국외 연구진
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