基于RNA-seq策略研究天然反义转录本的调控机制

项目名称： 基于RNA-seq策略研究天然反义转录本的调控机制

项目编号： No.31271386

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： 肖景发

作者单位： 中国科学院北京基因组研究所

项目金额： 80万元

中文摘要： 天然反义转录本(NATs)是由蛋白编码基因的反义链转录产生，属于一种特殊类型的非编码RNA, NATs具有多层次的调控活性，比如转录后调控、剪切调控和转运调控等，目前对于NATs的组成、功能和调控机制等方面的理解还有很大差距，因此亟需发展和应用深度测序技术揭示NATs的内在本质和调控机制。围绕上述科学问题，本项目拟以5种生殖相关的癌症细胞和3种正常细胞(卵巢细胞、乳腺细胞和乳腺上皮细胞)为研究对象，通过链特异性的RNA-seq方法构建癌症细胞和正常细胞的全景表达谱，研究天然反义RNA在肿瘤细胞发生过程中的作用，建立一套新的天然反义RNA的功能研究体系。最终目的是发现和鉴别一批与癌症相关的NATs，揭示其与肿瘤发生的关系及在不同肿瘤中的表达特征，阐明肿瘤发生过程中NATs的调控机制。发现以RNA分子为对象的治疗靶标和早期诊断标识，为肿瘤等重大疾病的防治提供新的思路和方法。

中文关键词： 天然反义转录本；宫颈癌；调控机制；转录组学；

英文摘要： Natural antisense transcripts (NATs) are coding or non-coding RNAs with sequence complementarity to other transcripts (sense transcripts). Natural antisense transcripts have already been found to function at several levels of eukaryotic gene regulation including translational regulation, RNA stability, alternative splicing, trafficking and genomic imprinting. Changes in antisense transcription have been implicated in pathogenesis, such as cancer or neurological disease. These RNAs could potentially regulate the expression of their sense partner(s) at either the transcriptional or post-transcriptional level through a variety of biological mechanisms, such as transcription interference, RNA masking, dsRNA-dependent mechanisms and directed remodeling of chromatin at target loci. While the majority of studies have focused on the mapping and evolutionary aspect of NATs and SAS pairs, only a few studies have interrogated and validated their abundance in different human tissue.There are still huge gaps in our understanding of NATs of mechanistic basis for their functions in cancer cell. Our aim is to investigate comprehensively the differential expression levels of SAS pairs between the normal and cancer cell based strand-specific massively parallel cDNA sequencing (RNA-seq) method. Strand-specific RNA-seq is a powerf

英文关键词： Natural Antisense Transcripts；cervical cancer；regulatory mechanism；transcriptomics；