Institut de Génomique Fonctionnelle de Lyon, UMR5242, Ecole Normale Supérieure de Lyon, Centre National de la Recherche Scientifique, Université Claude Bernard-Lyon 1, Lyon, France.
Wiley Interdiscip Rev RNA. 2023 Mar;14(2):e1752. doi: 10.1002/wrna.1752. Epub 2022 Jul 28.
Transcription factors (TFs) are present in all life forms and conserved across great evolutionary distances in eukaryotes. From yeast to complex multicellular organisms, they are pivotal players of cell fate decision by orchestrating gene expression at diverse molecular layers. Notably, TFs fine-tune gene expression by coordinating RNA fate at both the expression and splicing levels. They regulate alternative splicing, an essential mechanism for cell plasticity, allowing the production of many mRNA and protein isoforms in precise cell and tissue contexts. Despite this apparent role in splicing, how TFs integrate transcription and splicing to ultimately orchestrate diverse cell functions and cell fate decisions remains puzzling. We depict substantial studies in various model organisms underlining the key role of TFs in alternative splicing for promoting tissue-specific functions and cell fate. Furthermore, we emphasize recent advances describing the molecular link between the transcriptional and splicing activities of TFs. As TFs can bind both DNA and/or RNA to regulate transcription and splicing, we further discuss their flexibility and compatibility for DNA and RNA substrates. Finally, we propose several models integrating transcription and splicing activities of TFs in the coordination and diversification of cell and tissue identities. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Processing > Splicing Mechanisms.
转录因子（TFs）存在于所有生命形式中，并在真核生物中跨越巨大的进化距离得以保守。从酵母到复杂的多细胞生物，它们通过在不同的分子层面上协调基因表达，成为细胞命运决定的关键参与者。值得注意的是，TFs 通过协调表达和剪接水平的 RNA 命运来微调基因表达。它们调节可变剪接，这是细胞可塑性的一个重要机制，允许在精确的细胞和组织环境中产生许多 mRNA 和蛋白质同工型。尽管 TFs 在剪接中具有明显的作用，但 TFs 如何整合转录和剪接，最终协调多样化的细胞功能和细胞命运决定仍然令人费解。我们描绘了各种模式生物中的大量研究，强调了 TFs 在可变剪接中对于促进组织特异性功能和细胞命运的关键作用。此外，我们强调了最近描述 TFs 的转录和剪接活性之间分子联系的进展。由于 TFs 可以结合 DNA 和/或 RNA 来调节转录和剪接，我们进一步讨论了它们对 DNA 和 RNA 底物的灵活性和兼容性。最后，我们提出了几个模型，将 TFs 的转录和剪接活动整合到细胞和组织身份的协调和多样化中。本文属于以下类别：RNA 加工 > 剪接调控/可变剪接 RNA 与蛋白质和其他分子的相互作用 > 蛋白-RNA 相互作用：功能意义 RNA 加工 > 剪接机制。
