Alternative mRNA splicing enables the diversification of the proteome from a static genome and confers plasticity and adaptiveness on cells. Although this is often explored in development, where hard-wired programs drive the differentiation and specialization, alternative mRNA splicing also offers a way for cells to react to sudden changes in outside stimuli such as small-molecule metabolites. Fluctuations in metabolite levels and availability in particular convey crucial information to which cells react and adapt. We summarize and highlight findings surrounding the metabolic regulation of mRNA splicing. We discuss the principles underlying the biochemistry and biophysical properties of mRNA splicing, and propose how these could intersect with metabolite levels. Further, we present examples in which metabolites directly influence RNA-binding proteins and splicing factors. We also discuss the interplay between alternative mRNA splicing and metabolite-responsive signaling pathways. We hope to inspire future research to obtain a holistic picture of alternative mRNA splicing in response to metabolic cues.

选择性 mRNA 剪接使静态基因组中的蛋白质组多样化，并赋予细胞可塑性和适应性。尽管这在发育过程中经常被探索，其中硬连线程序驱动分化和专门化，但选择性 mRNA 剪接也为细胞提供了一种对外部刺激（如小分子代谢物）突然变化做出反应的方法。代谢物水平和可用性的波动尤其传达细胞反应和适应的关键信息。我们总结并强调了围绕 mRNA 剪接代谢调节的发现。我们讨论了 mRNA 剪接的生物化学和生物物理特性的基本原理，并提出了这些原理如何与代谢水平相交叉。此外，我们还提供了代谢物直接影响 RNA 结合蛋白和剪接因子的例子。我们还讨论了选择性 mRNA 剪接和代谢物响应信号通路之间的相互作用。我们希望激发未来的研究，以获得响应代谢线索的选择性 mRNA 剪接的整体情况。