Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
RNA Biol. 2024 Jan;21(1):42-51. doi: 10.1080/15476286.2024.2375097. Epub 2024 Jul 3.
The TATA-box binding protein (TBP) is the sole transcription factor common in the initiation complexes of the three major eukaryotic RNA Polymerases (Pol I, II and III). Although TBP is central to transcription by the three RNA Pols in various species, the emergence of TBP paralogs throughout evolution has expanded the complexity in transcription initiation. Furthermore, recent studies have emerged that questioned the centrality of TBP in mammalian cells, particularly in Pol II transcription, but the role of TBP and its paralogs in Pol I transcription remains to be re-evaluated. In this report, we show that in murine embryonic stem cells TBP localizes onto Pol I promoters, whereas the TBP paralog TRF2 only weakly associates to the Spacer Promoter of rDNA, suggesting that it may not be able to replace TBP for Pol I transcription. Importantly, acute TBP depletion does not fully disrupt Pol I occupancy or activity on ribosomal RNA genes, but TBP binding in mitosis leads to efficient Pol I reactivation following cell division. These findings provide a more nuanced role for TBP in Pol I transcription in murine embryonic stem cells.
TATA 框结合蛋白(TBP)是真核生物三种主要 RNA 聚合酶(Pol I、II 和 III)起始复合物中唯一共同的转录因子。尽管 TBP 是各种物种中三种 RNA Pols 转录的核心,但 TBP 同源物在进化过程中的出现扩展了转录起始的复杂性。此外,最近的研究质疑了 TBP 在哺乳动物细胞中的核心地位,特别是在 Pol II 转录中,但 TBP 和其同源物在 Pol I 转录中的作用仍有待重新评估。在本报告中,我们表明在鼠胚胎干细胞中,TBP 定位于 Pol I 启动子上,而 TBP 同源物 TRF2 仅弱结合 rDNA 的间隔启动子,表明它可能无法替代 TBP 进行 Pol I 转录。重要的是,急性 TBP 耗竭不会完全破坏 Pol I 在核糖体 RNA 基因上的占据或活性,但有丝分裂中的 TBP 结合导致细胞分裂后 Pol I 有效地重新激活。这些发现为 TBP 在鼠胚胎干细胞中 Pol I 转录中的作用提供了更细致的解释。