Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
Biochem J. 2024 Aug 7;481(15):999-1013. doi: 10.1042/BCJ20230410.
Temperature-dependent alternative splicing (AS) is a crucial mechanism for organisms to adapt to varying environmental temperatures. In mammals, even slight fluctuations in body temperature are sufficient to drive significant AS changes in a concerted manner. This dynamic regulation allows organisms to finely tune gene expression and protein isoform diversity in response to temperature cues, ensuring proper cellular function and physiological adaptation. Understanding the molecular mechanisms underlying temperature-dependent AS thus provides valuable insights into the intricate interplay between environmental stimuli and gene expression regulation. In this review, we provide an overview of recent advances in understanding temperature-regulated AS across various biological processes and systems. We will discuss the machinery sensing and translating temperature cues into changed AS patterns, the adaptation of the splicing regulatory machinery to extreme temperatures, the role of temperature-dependent AS in shaping the transcriptome, functional implications and the development of potential therapeutics targeting temperature-sensitive AS pathways.
温度依赖的可变剪接（AS）是生物体适应环境温度变化的关键机制。在哺乳动物中，即使体温稍有波动，也足以协同驱动显著的 AS 变化。这种动态调节使生物体能够根据温度线索精细地调整基因表达和蛋白质同工型多样性，确保细胞功能和生理适应的正常进行。因此，理解温度依赖的 AS 的分子机制为深入了解环境刺激与基因表达调控之间的复杂相互作用提供了有价值的见解。在这篇综述中，我们概述了在理解各种生物过程和系统中温度调节的 AS 方面的最新进展。我们将讨论感知温度线索并将其转化为 AS 模式变化的机制、剪接调控机制对极端温度的适应、温度依赖的 AS 在构建转录组中的作用、功能意义以及针对温度敏感的 AS 途径的潜在治疗方法的开发。
