一个从端粒组分衍生出的长链非编码RNA53在衰老中的作用研究

线粒体和端粒体系在衰老中都起着重要作用。最近的研究表明端粒体系和线粒体之间存在联系，协同在衰老中起作用。我们前期的初步研究结果表明：（1）从一个端粒组分衍生出的RNA400能以PNPASE依赖的方式进入线粒体，并在线粒体内被剪切加工成长链非编码RNA,命名为RNA53；（2）重要的是，RNA53随后又被转运出线粒体进入细胞质中；（3）细胞质中的RNA53能促进细胞衰老；（4）初步的衰老机制研究表明RNA53可能影响到线粒体的功能，例如线粒体膜电位降低、ATP合成下降、ROS水平升高等。本项目拟以RNA53为中心，围绕RNA53的剪切加工、转运、在细胞质中特异作用靶点以及参与调控的信号途径，深入研究参与这些过程的相关蛋白在衰老中的作用。此项研究对揭示LncRNA作为特异的信号分子参与线粒体逆行信号通路的机制、拓展对端粒体系和线粒体之间联系的认识、阐明衰老新机制，均有原创性的重要意义。

Both mitochondria and telomere play important role in aging. Recent studies indicate potential telomere-mitochondria connection which they can influence the state and function of each other and play synergistic role in aging. Our preliminary results suggest: (1)The RNA400 derived from one telomeric component can be imported into mitochondria and cleaved to be a long non-coding RNA (LncRNA) which named as RNA53. (2)Importantly, RNA53 is subsequently exported from mitochondria to cytosol. (3) Cytosolic RNA53 accelerates cellular senescence. (4) The mechanism studies indicate that RNA53 might cause mitochondrial dysfunction including of the decrease of mitochondrial membrane potential and ATP production, the increase of ROS level. In this study, we will focus on the RNA53 processing and export pathways, identify its binding partners in mitochondria and cytosol, explore its mediated mitochondrial retrograde pathway, and investigate the effect on aging of each related binding partners. This study will have original and creative significance in uncovering LncRNA as specific signaling transducer to mediate mitochondrial retrograde pathway, expanding the knowledge of telomere-mitochondria connection, and revealing novel mechanism of aging.