特殊结构新型长非编码RNA的系统发掘、进化表达及潜在功能研究

项目名称： 特殊结构新型长非编码RNA的系统发掘、进化表达及潜在功能研究

项目编号： No.31471241

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 杨力

作者单位： 中国科学院上海生命科学研究院

项目金额： 85万元

中文摘要： 越来越多的研究表明，人类基因组中存在大量长非编码RNA，其长度大于200 nt，但是缺乏蛋白编码能力。早期研究发现长非编码RNA在结构上与mRNA类似，通常具有5'端帽子和3'端poly(A)尾巴结构。近年来随着多种新技术体系的建立和应用，在体内发现了大量具有特殊结构的新型长非编码RNA，包括我们课题组发现的sno-lncRNA和一类环形RNA。本申请项目在我们已有的研究基础上，进一步完善全新转录组测序和计算分析流程，针对多个物种转录组开展研究，系统全面地发掘上述多种特殊结构新型长非编码RNA及其在不同物种中的表达差异；深入解析其在进化过程中的序列/结构演变规律，寻找与其相互作用的蛋白因子等，以揭示其在不同物种中的重要功能作用；进一步有针对性地对其成熟机制及其重要功能开展预测并进行深入实验研究，为全面理解基因组中大量存在的长非编码RNA序列在物种进化过程中的发生规律及其作用提供理论基础。

中文关键词： 计算生物学；高通量测序；非编码RNA；转录组学；比较基因组学

英文摘要： Growing lines of evidence have indicated that genomes are pervasively transcribed, with many previously ignored portions of the genome transcribed as long noncoding RNAs. Long non-coding RNAs (lncRNAs) are non-protein-coding RNAs and larger than 200 nucleotides. Many lncRNAs have the similar structure with mRNAs, normally 5' capped and 3' polyadenylated. With the advent of high-throughput technologies, many lncRNAs were recently identified with specific structures, but lack of polyadenylation and/or capping, including MALAT1/NEAT1、sno-lncRNA and at least two types of circular RNAs. We have recently developed new experimental and computational pipelines to systematically profile some aforementioned lncRNAs without typical polyadenylated structures. In the current proposal, we will further modify these pipelines to genome widely profile these structured lncRNAs from human, non-human primates and mouse and compare their expression differences across species. In addition, we are planning to identify the specific sequences/motifs/structures for these lncRNA during evolution with comparative genomics to find their drive force for evolution. We will further computationally predict potential protein factors that bind to these lncRNAs and further prove it with in vitro assays, which will give molecular clues for their potential functions in different species. Finally, we will also perform loss-of-function and gain-of-function studies with specific structured lncRNAs to further detect their regulatory roles in the whole transcriptomic levels. The knowledge can provide a clear insight into functional importance of these structured lncRNAs during evolution.

英文关键词： Computational Biology;High Throughput Sequencing;Noncoding RNA;Transcriptomics;Comparative Genomics