脳発達におけるリボソーム生合成の新たな制御機構を解明(Researchers Uncover Novel Mechanism for Regulating Ribosome Biogenesis During Brain Development)

2025-06-30 中国科学院(CAS)

<関連情報>

• https://english.cas.cn/newsroom/research_news/life/202506/t20250625_1046179.shtml
• https://www.science.org/doi/10.1126/sciadv.adq9643

VIRMAを介したm6A修飾はリボソーム生合成の調節を通して前脳形成を制御する VIRMA-mediated m6A modification regulates forebrain formation through modulating ribosome biogenesis

Min Wu, Xiaoli Wu, Haifeng Sun, Wen Wang, […] , and Tao Zhou
Science Advances  Published:27 Jun 2025
DOI:https://doi.org/10.1126/sciadv.adq9643

Abstract

N⁶-Methyladenosine (m⁶A) modification plays crucial roles in tissue development and homeostasis. However, the mechanisms underlying cellular adaptation of m⁶A modification and their impact on protein synthesis machinery remain unclear. VIRMA, the largest and evolutionarily conserved core of the m⁶A methyltransferase complex, is highly expressed in the embryonic brain and various cancers. Here, we demonstrate that VIRMA-mediated m⁶A modification is essential for active ribosome biogenesis. VIRMA depletion destabilizes the entire writer complex and reduces m⁶A levels, leading to decreased proliferation and increased apoptosis of neural progenitor/stem cells, ultimately causing severe forebrain developmental defects. Mechanistically, VIRMA depletion impairs ribosome biogenesis by inhibiting mRNA decay, triggering a p53-dependent stress response and compromising global protein synthesis. These findings extend to some cancer cells, suggesting a potential conservation of this mechanism. Overall, our study reveals the critical role of m⁶A in adapting protein synthesis machinery during brain development.