Pan-cancer survey of candidate non-coding RNA transcripts on the cloud using a targeted de novo assembly approach

使用靶向从头组装方法在云上对候选非编码 RNA 转录本进行泛癌调查

• 批准号: 9167382
• 负责人: Inanc Birol
• 金额: $ 4.32万
• 依托单位: BRITISH COLUMBIA CANCER AGENCY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-17 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9167382
• 关键词: 3' Untranslated Regions; Adopted; Amino Acid Sequence; Binding Sites; Bioinformatics; Biological; Cleavage And Polyadenylation Specificity Factor; Communities; Computer software; DNA; Data; Data Set; Development; Disease; Elements; Enzymes; Event; Funding; Genes; Genetic Transcription; Genomics; Goals; Guidelines; Health; High-Throughput Nucleotide Sequencing; Human; Investigation; Investments; Laboratories; Large-Scale Sequencing; Lead; Literature; Location; Malignant Neoplasms; Messenger RNA; Methods; MicroRNAs; Molecular Profiling; Mutation; Peptide Sequence Determination; Physiological; Play; Poly A; Poly(A) Tail; Polyadenylation; Positron-Emission Tomography; Process; Property; Proteins; Protocols documentation; RNA; RNA Processing; Reading; Recruitment Activity; Reporting; Research Personnel; Resource Sharing; Role; Running; Sampling; Site; Surveys; Tail; Technology; The Cancer Genome Atlas; Time; Transcript; Transcriptional Regulation; Translating; United States National Institutes of Health; Untranslated RNA; Untranslated Regions; Validation; Work; cancer risk; cancer subtypes; cohort; cost; experience; high standard; improved; method development; reference genome; research study; tool; transcriptome; transcriptome sequencing

DESCRIPTION (provided by applicant): When a gene is activated, it is copied ("transcribed") from DNA into a string of molecules called a messenger RNA (mRNA). The middle section of each mRNA encodes the information that is translated into the corresponding protein sequence; the two ends, called untranslated regions (UTRs), play a number of other important roles. This proposal concerns the tail end of the mRNA, known as the 3' UTR, which helps to regulate the stability and location of the mRNA and the amount of the corresponding protein that is produced. The point at which the transcription of a given mRNA ends is determined by the presence of a sequence called a polyadenylation site. Some genes have more than one such site, meaning that there can be two or more different forms of the corresponding mRNA, with different 3' UTRs and therefore different levels of activity. Changes in the ratio of the different forms are thought to contribute to the development of a range of disorders, including some cancers. The methods currently used to study polyadenylation require an extra set of experiments to be run, which is expensive and slow. However, Drs. Birol and Karsan and their teams have obtained evidence that polyadenylation can be studied alongside other important types of transcriptional regulation, using data from experiments that are already performed as part of standard analysis. This will make studies of polyadenylation sites affordable by more laboratories, and will add value to existing data.

描述（由申请人提供）：当基因被激活时，它会从 DNA 复制（“转录”）成一串称为信使 RNA (mRNA) 的分子。每个mRNA的中间部分编码翻译成相应蛋白质序列的信息；两端称为非翻译区 (UTR)，发挥着许多其他重要作用。该提案涉及 mRNA 的尾端，即 3' UTR，它有助于调节 mRNA 的稳定性和位置以及产生的相应蛋白质的量。给定 mRNA 的转录结束点由称为聚腺苷酸化位点的序列的存在决定。有些基因具有多个这样的位点，这意味着可能存在两种或多种不同形式的相应 mRNA，具有不同的 3' UTR，因此具有不同的活性水平。不同比例的变化 人们认为这些形式会导致一系列疾病的发生，包括一些癌症。目前用于研究聚腺苷酸化的方法需要进行一组额外的实验，这是昂贵且缓慢的。然而，博士。 Birol 和 Karsan 及其团队已经获得证据，表明多腺苷酸化可以与其他重要类型的转录调控一起研究，使用已经作为标准分析一部分进行的实验数据。这将使更多实验室能够负担得起聚腺苷酸化位点的研究，并将增加现有数据的价值。

项目成果

Recurrent tumor-specific regulation of alternative polyadenylation of cancer-related genes.

• DOI: 10.1186/s12864-018-4903-7
• 发表时间: 2018-07-13
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Xue Z;Warren RL;Gibb EA;MacMillan D;Wong J;Chiu R;Hammond SA;Yang C;Nip KM;Ennis CA;Hahn A;Reynolds S;Birol I
• 通讯作者: Birol I