Isoform usage as a distinct regulatory layer driving nutrient-responsive metabolic adaptation

IF 27.7 1区生物学 Q1 CELL BIOLOGY

Cell metabolism Pub Date : 2025-02-11 DOI:10.1016/j.cmet.2025.01.009

Jia Li, Chaoqun Cai, Wei Wen Teo, Kai Shin Chin, Yadanar Than Naing, Shengren Song, Franklin Nelson, Li Qiang, Dan Xu, Lei Sun

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引用次数: 0

Abstract

Transcriptome modulation is essential for metabolic adaptation to nutrient environments. However, the role of isoform usage, a crucial transcriptome component, is not yet fully understood. This study outlines the landscape of isoform-usage modulations across major metabolic organs in both mice and monkeys, spanning diverse metabolic states. Our in-depth analysis identifies numerous isoform-usage events, intricately influenced by nutrient challenges and largely independent of gene expression regulation. Comparative analyses of mice and monkeys highlight hundreds of conserved isoform events that exhibit consistent responses to nutrient challenges across species and correlate with human metabolic traits. When analyzing splicing factor-binding motifs in nutrient-regulated events, HuR emerges as the predominant orchestrator of the isoform network in adipocytes, which is validated using an adipose tissue-specific knockout and an Ap2-promoter-driven transgenic mouse model. In summary, our results offer a comprehensive perspective on isoform usage in metabolic regulation, setting a platform for future functional inquiries.

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异构体的使用作为一个独特的调控层驱动营养反应性代谢适应

转录组调节对营养环境的代谢适应至关重要。然而，异构体使用的作用，一个关键的转录组成分，尚未完全了解。本研究概述了小鼠和猴子主要代谢器官中异构体使用调节的景观，跨越不同的代谢状态。我们的深入分析确定了许多异构体使用事件，这些事件错综复杂地受到营养挑战的影响，并且在很大程度上独立于基因表达调控。对小鼠和猴子的比较分析强调了数百个保守的异构体事件，这些事件对不同物种的营养挑战表现出一致的反应，并与人类的代谢特征相关。在分析营养调节事件中的剪接因子结合基序时，HuR成为脂肪细胞中同种异构体网络的主要协调者，这一点通过脂肪组织特异性敲除和ap2启动子驱动的转基因小鼠模型得到了验证。总之，我们的研究结果为代谢调节中异构体的使用提供了一个全面的视角，为未来的功能研究奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell metabolism 生物-内分泌学与代谢

CiteScore

48.60

自引率

1.40%

发文量

173

审稿时长

2.5 months

期刊介绍： Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others. Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.