一类内含子来源的长非编码RNA的加工成熟机制及功能研究

项目名称： 一类内含子来源的长非编码RNA的加工成熟机制及功能研究

项目编号： No.31271376

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 陈玲玲

作者单位： 中国科学院上海生命科学研究院

项目金额： 90万元

中文摘要： 长非编码RNA（lncRNA）是以长链RNA（>200核苷酸）形式发挥功能的非编码生物大分子，广泛参与调控一系列细胞的重要功能。我们最近发现一类新型内含子来源的lncRNAs（id-lncRNAs）。已有研究结果表明，它们在干细胞中高表达，其基因所在染色体区域提示与遗传疾病Prader-Willy Syndrome（PWS）相关；同时它们富集并形成特殊的细胞核亚结构，提示具有重要的生物学功能。本申请项目主要是在以上研究基础上，深入探索这些新型id-lncRNAs的分子特性(结构、细胞核内定位等变化特性)、转录加工机制（特异性转录、抗RNA酶降解等特征机制）和相应的生物学功能（核亚结构、干细胞干性维持等相关功能），为进一步了解长非编RNA的来源、加工等提供新的理论依据和对真核生物转录组提供更丰富的认识，为干细胞多能性维持研究提供一种新的RNA水平调控思路，为PWS综合症研究拓展新的方向。

中文关键词： 非polyA 结尾的RNA；长非编码RNA；sno-lncRNA；环形RNA；SPA

英文摘要： Long noncoding RNAs (lncRNAs) are mRNA-like, non-protein-coding RNAs that are pervasively transcribed throughout eukaryotic genomes. Rather than silently accumulating in the nucleus, we now know that many lncRNAs play important roles in biological processes. We have recently used deep sequencing to explore the repertoire of non-polyadenylated RNAs from HeLa cells and H9 human embryonic stem cells (hESCs), and have discovered a new class of non-polyadenylated lncRNAs that is derived from introns (we name them id-lncRNAs). This proposal is to study them in greater detail. Such RNAs can be found in many cell types examined so far, and appear to be widely expressed in human tissues. Further, the genomic region encoding some of the most abundant of these RNAs is highly enriched in hESCs and is also specifically deleted in human genetic disorder, Prader-Willi Syndrome (PWS), thus implicating these molecules in an important human disease. We will characterize how id-lncRNAs are made and what proteins associate with them. In addition, we will ask what they do in cells and begin to address their possible roles in PWS. In the first aim, we will characterize the sequences and motifs that are required for id-lncRNAs formation and also examine the expression of id-lncRNAs. We will also investigate their sub-nuclear localizat

英文关键词： non-polyadenylated RNA；long noncoding RNA；sno-lncRNA；circular RNA；SPA