越来越多的研究表明，长非编码RNA的关键功能作用与其正确的亚细胞定位密切相关。细胞核定位长非编码RNA主要是在表观遗传、转录以及核亚结构产生等水平发挥作用；而细胞质定位的长非编码RNA则主要在转录后水平发挥作用、甚至在特殊情况下可以产生短肽发挥功能。但是，对长非编码RNA的亚细胞定位、及其与功能的相关性研究迄今仍处于起步阶段。本申请项目通过进一步完善高精准度的亚细胞组分分离技术，并结合高通量测序和计算生物学分析体系，针对不同亚细胞组分的转录组长非编码RNA开展系统研究，以期全面揭示长非编码RNA的亚细胞定位及其动态变化规律，阐明长非编码RNA亚细胞差异定位的调控机制，构建长非编码RNA亚细胞定位及其功能的相关性图谱；进一步利用公共数据，对长非编码RNA的亚细胞定位与疾病发生的关联性展开分析。为深入揭示亚细胞定位对于长非编码RNA功能发挥、及其与疾病发生之间的关系研究提供坚实的理论基础。

Accumulated lines of evidence have suggested that the proper subcellular localization of long noncoding RNAs (lncRNAs) is important for their correct functions. For example, nuclear lncRNAs can regulate gene expression at epigenetic and transcriptional levels. In addition, some nuclear lncRNAs also function as scaffold molecules to assemble nuclear bodies. Differently, cytoplasm lncRNAs in general play biological roles in the post-transcriptional level. Strikingly, some lncRNAs can even translate small peptides to involve in regulation. Nevertheless, the molecular mechanism of subcellular localization of lncRNAs and their dynamic regulation during differentiation or other processes have not yet been well studied. We will apply new methodologies of subcellular RNA fractionations, combined with next generation deep sequencing and computational analyses, to comprehensively annotate the subcellular distribution of lncRNAs among human stem cells and their neuronal differentiation. Importantly, we will systemically correlate the dynamic of lncRNA subcellular localization to their corresponding biological functions. Furthermore, we will also inspect the detailed molecular mechanisms of how the subcellular localization of lncRNAs affects their function, especially in pathology of human diseases. All these studies will provide a molecular basis for lncRNAs subcellular localization and their corresponding functions in both physiology and pathology.