线粒体基因组来源的长非编码RNA通过与p53蛋白的相互作用调控细胞核基因的表达

项目名称： 线粒体基因组来源的长非编码RNA通过与p53蛋白的相互作用调控细胞核基因的表达

项目编号： No.31671347

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 李灵

作者单位： 四川大学

项目金额： 25万元

中文摘要： 细胞核基因组和线粒体基因组之间存在着严密的相互调控关系。除了蛋白质和miRNA，新近研究显示核基因来源的lncRNA也能够调节线粒体功能。然而，线粒体基因组是否能够转录产生功能性lncRNA，这些lncRNA是否能够逆向调控核基因的表达却不得而知。lncRNA通过与蛋白质的相互作用调控基因表达是其发挥生物学功能的重要途径。我们在前期研究中利用自主建立的RNA-SELEX技术筛选到一条与p53蛋白结合、且由线粒体基因组转录的lncRNA，mtlncRNA。初步研究显示mtlncRNA通过抑制p53的四聚化使p53丧失与靶基因启动子结合的能力，从而抑制p21等靶基因的转录，并影响细胞周期的G1/S转换。基于现有基础，本项目将深入研究mtlncRNA对核基因表达的逆向调控和调控机制；并将以细胞周期及细胞凋亡调控为切入点，探讨mtlncRNA在H2O2诱导的氧化应激中的意义。

中文关键词： 线粒体基因组；长非编码RNA；p53蛋白；细胞核基因；基因表达调控

英文摘要： There is a crosstalk between nucleus and mitochondria, which is established by the coordinated regulation between nuclear and mitochondrial genomes. In addition to miRNA and protein factors, specific nuclear-derived lncRNAs have also been implicated in the regulation of mitochondrial network. However, whether the mitochondrial genome encodes functional lncRNAs, as well as whether the mitochondrial lncRNAs operate in the regulation of nuclear genes, remains to be elucidated. Most of the characterized lncRNAs achieve their biological functions by controlling gene expression, and their interaction with protein is a well-established action mode. With a RNA-SELEX procedure, we have isolated a p53-binding lncRNA, which is encoded by the mitochondrial genome and referred to as mtlncRNA. An interaction between mtlncRNA and p53 inhibits formation of the p53 tetramer, resulting in the loss of its DNA binding activity and repression of p53 targets that include p21. Moreover, mtlncRNA can influence the cell cycle transition from G1 to S phase. These preliminary results prompt the current project to further decode the role of mtlncRNA in controlling nuclear genes. Furthermore, we will determine the regulatory effects of mtlncRNA on cell cycle and apoptosis in the case of H2O2-induced oxidative stress.

英文关键词： mitochondrial genome;long noncoding RNA;p53 protein;nuclear gene;regulation of gene expression