Working Backwards from the Proteome

从蛋白质组逆向研究

• 批准号: 7926897
• 负责人: DOUGLAS F. LAKE
• 金额: $ 29.68万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-04 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7926897
• 关键词: Cell Line; Cells; Code; Complex; Data; Databases; Gene Expression Profile; Genes; Genome; Human; Maps; Mass Spectrum Analysis; Peptides; Play; Poly(A)+ RNA; Proteins; Proteome; Proteomics; RNA; Reporting; Role; Thinking; Transcript; Translating; Work; public health relevance

DESCRIPTION (provided by applicant): The ENCODE consortium analyzed RNA produced from 1% of the genome. They reported that the transcriptome is incredibly complex, and that approximately 93% of the genome is transcribed into RNA. The current paradigm is that this RNA is "non-protein- coding" and likely plays an unknown regulatory role in the cell. We hypothesize that much of this RNA is not only transcribed, but also translated into protein. To support our hypothesis, we bioinformatically translated into protein the RNA that ENCODE discovered and used it to construct a database for searching mass spectra derived from the proteome of five different cell lines. By starting with the proteome and working backwards toward RNA, we have preliminary data indicating that polyadenylated RNA transcripts from intergenic space are translated. We propose to discover and identify peptides and small proteins translated from ENCODE RNA (1% of genome, 30Mb) and to create a proteomic map that helps connect the proteome to the transcriptome. It would also help clarify the complexities of the transcriptome. If our hypothesis proves correct, it would change current thinking about intergenic space, gene number and provide an opportunity to study new genes and new proteins with new functions. PUBLIC HEALTH RELEVANCE: In humans, the number of genes was estimated to be much higher than the current ~21,000 gene estimate. Because of recent discoveries that the genome is pervasively transcribed, we believe that much of the RNA in a cell is also translated into protein. If true our findings would fuel the discoveries of many new genes with new functions.

描述（由申请人提供）：从1％的基因组产生的编码联盟分析的RNA。他们报告说，转录组非常复杂，大约93％的基因组被转录为RNA。当前的范式是该RNA是“非蛋白质编码”，并且可能在细胞中起未知的调节作用。我们假设大部分RNA不仅被转录，而且被翻译成蛋白质。为了支持我们的假设，我们将生物信息转化为蛋白质的RNA，该RNA编码发现并使用它来构造一个数据库，以搜索从五个不同细胞系的蛋白质组衍生的质谱。通过从蛋白质组开始并向RNA进行后退，我们获得了初步数据，表明来自基因间空间的聚腺苷酸化RNA转录物被翻译。我们建议从编码RNA（基因组的1％，30MB）转化并鉴定肽和小蛋白质，并创建有助于将蛋白质组连接到转录组的蛋白质组学图。这也将有助于阐明转录组的复杂性。如果我们的假设被证明是正确的，它将改变有关基因间空间，基因数的当前思维，并提供了研究新基因和具有新功能的新蛋白质的机会。公共卫生相关性：在人类中，估计基因的数量远高于当前约21,000个基因估计值。由于最近发现基因组被普遍转录，我们认为细胞中的大部分RNA也会转化为蛋白质。如果是正确的，我们的发现将推动许多新功能的新基因的发现。