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mTOR信号通路对转录组可塑性的调控。

Regulation of transcriptome plasticity by mTOR signaling pathway.

作者信息

Yong Jeongsik, Kim Hyunjoo, Lee Euyeon, Jung Yoonju

机构信息

Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, Minneapolis, MN, USA.

Department of Chemical Engineering and Material Sciences, University of Minnesota Twin Cities, Minneapolis, MN, USA.

出版信息

Exp Mol Med. 2025 Aug 14. doi: 10.1038/s12276-025-01508-y.

Abstract

The mechanistic target of rapamycin (mTOR) pathway, long recognized for its critical roles in cellular metabolism and growth, is increasingly appreciated for its regulatory impact on the transcriptome. Recent insights into mTOR's regulation of alternative splicing and polyadenylation reveal a sophisticated mechanism by which mTOR influences RNA processing to affect the proteome's diversity and functionality. Here, in this Review, we delve into the multifaceted roles of mTOR in modulating transcriptome plasticity, highlighting its influence beyond traditional functions such as protein synthesis and cell growth. By examining the latest findings, we explore how mTOR-mediated transcriptome plasticity plays a pivotal role in cellular adaptation and pathogenesis. Studies indicate that mTOR modulation of RNA processing pathways enables cells to respond dynamically to environmental and metabolic cues, thereby altering protein function and cellular behavior in a context-dependent manner. This capability is crucial for both normal physiological responses and the development of disease. The Review also discusses the implications of these findings for understanding complex biological systems and diseases, particularly cancer, where mTOR's regulation of transcript diversity could drive tumor heterogeneity and treatment resistance. As research continues to uncover the extensive influence of mTOR on RNA processing, it becomes clear that a comprehensive understanding of these mechanisms is essential for the development of targeted therapies and the prediction of their outcomes in clinical settings.

摘要

雷帕霉素作用机制靶点(mTOR)通路长期以来因其在细胞代谢和生长中的关键作用而被认可,如今其对转录组的调控影响也越来越受到重视。最近对mTOR在可变剪接和多聚腺苷酸化调控方面的见解揭示了一种复杂机制,通过该机制mTOR影响RNA加工,从而影响蛋白质组的多样性和功能。在本综述中,我们深入探讨mTOR在调节转录组可塑性方面的多方面作用,强调其超越蛋白质合成和细胞生长等传统功能的影响。通过研究最新发现,我们探讨mTOR介导的转录组可塑性如何在细胞适应和发病机制中发挥关键作用。研究表明,mTOR对RNA加工途径的调节使细胞能够动态响应环境和代谢信号,从而以上下文依赖的方式改变蛋白质功能和细胞行为。这种能力对于正常生理反应和疾病发展都至关重要。本综述还讨论了这些发现对于理解复杂生物系统和疾病(特别是癌症)的意义,在癌症中mTOR对转录多样性的调节可能驱动肿瘤异质性和治疗抗性。随着研究不断揭示mTOR对RNA加工的广泛影响,显然全面理解这些机制对于开发靶向治疗方法以及预测其在临床环境中的疗效至关重要。

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