TBP facilitates RNA Polymerase I transcription following mitosis

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盒结合蛋白（TATA-box binding protein, TBP）是三种主要真核RNA聚合酶（Pol I、Pol II、Pol III）的起始复合物中共有的唯一转录因子。尽管在不同物种中，TBP都是这三类RNA聚合酶介导转录的核心因子，但进化过程中TBP旁系同源物的出现，增加了转录起始的复杂性。此外，近期已有研究对TBP在哺乳动物细胞中的核心地位提出了质疑，尤其是在Pol II转录过程中，但TBP及其旁系同源物在Pol I转录中的作用仍有待重新评估。本研究证实，在鼠胚胎干细胞中，TBP可定位于Pol I启动子区域；而TBP的旁系同源物TRF2仅能弱结合核糖体DNA（rDNA）的间隔启动子，这提示其无法替代TBP参与Pol I转录。值得注意的是，急性TBP耗竭并未完全破坏Pol I在核糖体RNA基因上的结合或活性，但TBP在有丝分裂中的结合可促使细胞分裂后Pol I高效重新激活。上述研究结果为鼠胚胎干细胞中TBP在Pol I转录中的作用提供了更为精细的阐释。