无义介导降解机制的新靶标——非编码转录本？

项目名称： 无义介导降解机制的新靶标——非编码转录本？

项目编号： No.31471224

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 孔祥银

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： 无义介导降解作为一种机体的RNA监督机制，主要负责识别并且降解那些因为含有提前终止密码子而无法完整翻译的转录本，保证机体生命活动的正常进行。目前仅知道可编码的转录本能够通过该机制进行调控，而并不清楚占人基因组达70%的非编码基因的转录本是否具有类似的质量控制过程。与可编码的转录本相比，很多非编码转录本具有一些相似的特点，比如其经常有一个到多个开放阅读框，同时核糖体印迹测序技术发现核糖体可以结合在非编码RNA上。另外一些非编码转录本，比如长链非编码RNA等在剪切成熟后，也需要将外显子连接复合物一一清除。我们前期实验和信息分析发现，抑制NMD核心因子后，lincRNA转录本整体的表达上升, 据此我们推测非编码转录本也可能受NMD机制调控。在本项目中，我们拟通过多种实验和信息分析手段研究无义介导降解机制对非编码转录本的调控作用，并进一步研究其在疾病发生中的作用。

中文关键词： 非编码RNA；无义介导降解机制；表达调控

英文摘要： Nonsense mediated decay (NMD) is a RNA surveillance mechanism， which involved in detection and decay of transcripts with premature termination codons (PTC). PTC from transcripts may cause organisms to produce truncated proteins.The decay of such transcripts can ensure the normal function of organism. Current studies about NMD targets mainly focus on mRNAs, and it's still unclear whether noncoding RNAs can be regulated by NMD pathway. Many non-coding RNAs have some features that are similar to coding transcripts, for example: the muture noncoding RNAs may have one or more small open reading frames (ORF); and results from ribosome profiling technology indicate that ribosome can bind with noncoding RNAs. Furthermore, many noncoding RNAs, especially those long noncoding RNAs, should clean all those exon junction complexes (EJCs) after the splicing process. We recently found that the expression level of many long noncoding transcripts increased after knockdown NMD factor Upf1. Thus, we speculate that long noncoding RNAs may also be degraded by NMD mechanism. In this project, we will use different experimental and bioinformatic methods to investigate whether NMD also regulate non-coding transcripts. At last, we plan to explore the role of candidate non-coding NMD targets in human diseases.

英文关键词： non-coding RNA;nonsense-mediated decay mechanism;regulation of expression