裂殖酵母亚精胺核糖开关调控机制的研究

Spermidine is widely spread in living cells, and only small amout of spermidine can surport cell life. Spermidine is related with human diseases such as aging, cancer etc, which is regulated at the level of RNA. Riboswitches are functional RNAs located in UTR of mRNA, which can specifically bind to small molecule and regulate downstream gene expression.In this project, we will employ in vitro translation, crystal structure etc.to address the structual changes of a new class of riboswitch specifically sensing spermidine in 3D level, and its underlying molecular mechanism of gene regulation. By revealing the mechanism of gene regulation of this newly found riboswitch in fission yeast, we will further study the importance of spermidine sensing riboswitch that participates a pivotal eukaryotic metabolic process.Due to its essential cellular functions, the research will also provide new insight for research and strategy of the clinic treatment.

亚精胺在细胞中普遍存在，仅仅微量的亚精胺就可以维持细胞的正常生长。亚精胺是多胺代谢途径的关键成分，与癌症、衰老等人类疾病密切相关，它在细胞内的调控主要集中在RNA水平上。核糖开关是一种较新的调控方式，在原核生物中较为普遍，而在真核生物中极少被发现。它是一类可以特异性的结合小分子配体并调控相关基因表达的功能RNA，一般位于mRNA的非编码区。本项目试图利用体外翻译、晶体解析等重要手段，揭示裂殖酵母中的新型核糖开关-亚精胺核糖开关的在三维构象中的结构变化及基因调控的分子机制。本项目通过解析亚精胺这一真核生物核糖开关基因调控机制，深入研究裂殖酵母中亚精胺核糖开关作为一种新的基因调控方式，参与真核生物关键代谢途径中基因的调控，在真核生物中发挥的重要功能。由于亚精胺所参与的多胺代谢途径对细胞的正常生理功能至关重要，对于这一新型核糖开关的研究也将为治疗癌症、衰老等人类重大疾病的临床研究提供理论依据。

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