eIF4G2-Mediated Translation Initiation of Histone Modifiers Is Essential for Intestinal Stem Cell Maintenance and Differentiation

Haruko Kunitomi; Aye Myat Khaine; Radia Jamee; Vanessa Arreola; Mariselle Lancero; Amba Raychaudhuri; Samuel David Perli; Yoshiko Sato; Mio Iwasaki; Pedro Ruivo; Kiichiro Tomoda; Mari Mito; Yuichi Shichino; Shintaro Iwasaki; Shinya Yamanaka

doi:10.1101/2025.05.19.652834

Cell BiologybioRxivMay 19, 2025

Preprint

eIF4G2-Mediated Translation Initiation of Histone Modifiers Is Essential for Intestinal Stem Cell Maintenance and Differentiation

Haruko Kunitomi iD, Aye Myat Khaine iD, Radia Jamee iD, Vanessa Arreola, Mariselle Lancero iD, Amba Raychaudhuri iD, Samuel David Perli iD, Yoshiko Sato iD, Mio Iwasaki iD, Pedro Ruivo iD, Kiichiro Tomoda iD, Mari Mito iD, Yuichi Shichino iD, Shintaro Iwasaki iD, Shinya Yamanaka iD

Abstract

eIF4G2 (also known as NAT1, p97, or DAP5) is an evolutionally conserved protein homologous to the C-terminal two-thirds portion of eukaryotic translation initiation factor (eIF) 4G. Despite its abundant and ubiquitous expression, the physiological and pathological functions of eIF4G2 are poorly understood. Here, we show that acute loss of eIF4G2 in adult mice results in rapid weight loss with abnormalities in multiple organs, including impaired maintenance and differentiation of intestinal stem cells. Genome-wide ribosome profiling revealed that eIF4G2 is critical for the translation of key histone modification proteins involved in intestinal stemness. Our study underscores the importance of eIF4G2-mediated translation initiation in multicellular organisms.

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