Ubiquitination and deubiquitination of 4E-T regulate neural progenitor cell maintenance and neurogenesis by controlling P-body formation

作者：Shreeya Kedia, Mohamad‐Reza Aghanoori, Kaylan M.L. Burns, Maneesha Subha, Laura Williams, Pengqiang Wen, Drayden Kopp, Sarah L. Erickson, Emily M. Harvey, Xin Chen, Michelle Hua, Jose Uriel Perez, Md. Fatin Ishraque, Guang Yang · 发表于：Cell Reports · 年份：2022 · DOI：10.1016/j.celrep.2022.111070 · 被引用次数：12 · 研究领域：Ubiquitin and proteasome pathways、RNA modifications and cancer、Epigenetics and DNA Methylation

During embryogenesis, neural stem/progenitor cells (NPCs) proliferate and differentiate to form brain tissues. Here, we show that in the developing murine cerebral cortex, the balance between the NPC maintenance and differentiation is coordinated by ubiquitin signals that control the formation of processing bodies (P-bodies), cytoplasmic membraneless organelles critical for cell state regulation. We find that the deubiquitinase Otud4 and the E3 ligase Trim56 counter-regulate the ubiquitination status of a core P-body protein 4E-T to orchestrate the assembly of P-bodies in NPCs. Aberrant induction of 4E-T ubiquitination promotes P-body assembly in NPCs and causes a delay in their cell cycle progression and differentiation. In contrast, loss of 4E-T ubiquitination abrogates P-bodies and results in premature neurogenesis. Thus, our results reveal a critical role of ubiquitin-dependent regulation of P-body formation in NPC maintenance and neurogenesis during brain development.