rRNA的转录是核糖体合成的限速步骤，被严谨调控。rRNA转录的调控分子在rRNA单基因拷贝和表观遗传学水平多层次参与对rRNA转录的调控。rRNA转录调控分子如何调控rDNA的表观遗传学水平，代谢应激信号下它们的功能变化是此领域的研究热点。Apak是我们前期证实的一种选择性抑制p53凋亡功能的KZNF分子，它能定位在核仁以p53不依赖的方式抑制rRNA的转录。在代谢应激状态下，激活的AMPK通路促进核质中Apak和DBC1的解离，向核仁移位，抑制rRNA的转录。本申请中，我们将通过Apak与rDNA结合序列的确证，核仁中相互作用分子的鉴定在表观遗传学水平探讨Apak调控rRNA转录的机制。同时进一步确证代谢应激信号通过Apak向rRNA转录传递的信号通路。此项工作将增进对rRNA调控的了解，完善AMPK在rRNA调控中的功能，为细胞感应应激信号对rRNA的调控机制提供新的解释。

Transcription of ribosomal RNA (rRNA) by the nucleolar RNA polymerase I (Pol I) represents the rate-limiting step in ribosome synthesis, and should be finely regulated. rRNA transcription is regulated by its regulators at different layer of rRNA single-copy and epigenetics levels. How the regulators modulate rDNA epigenetic state and its function changes under metabolic stress are the hotspots of this area and not fully elucidated. In our previous work, we demonstrated Apak, one of KZNF family member, selectively inhibit p53-mediated apoptosis, and nucleolus-located Aapk could inhibit rRNA transcription in a p53-independent manner. Under metabolic stress, the activated AMPK pathway promotes the dissociation of nucleoplasm- located Apak and DBC1, enhances the nucleolus-location and rRNA transcription repression of Apak. In this program, we will confirm the binding sites of Apak on rDNA, identify the interaction protein of Apak in nucleolus, and explore the repression mechanism of Aapk on rRNA transcription at the epigenetic level. At the same time, we will further confirm the signal pathway from which metabolic stress signal transduces to rRNA transcription dependence of Apak. This work will provide key insight into understanding of rRNA regulation and AMPK function in rRNA transcription regulation, reveal the regulation mechanism of cell response stress response on rRNA transcription.