Working Backwards from the Proteome

描述（由申请人提供）：ENCODE联盟分析了从1%基因组中产生的RNA。他们报告说，转录组非常复杂，大约93%的基因组被转录成RNA。目前的范式是，这种RNA是“非蛋白质编码”，可能在细胞中起着未知的调节作用。我们假设，这些RNA中的大部分不仅被转录，而且还被翻译成蛋白质。为了支持我们的假设，我们将ENCODE发现的RNA生物信息学翻译成蛋白质，并将其用于构建一个数据库，用于搜索来自五种不同细胞系蛋白质组的质谱。通过从蛋白质组开始并向后研究RNA，我们有初步的数据表明来自基因间空间的多聚腺苷酸化RNA转录物被翻译。我们建议发现和鉴定从ENCODE RNA（基因组的1%，30Mb）翻译的肽和小蛋白，并创建一个蛋白质组图谱，帮助连接蛋白质组和转录组。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，这将改变目前对基因间隔、基因数量的看法，并为研究具有新功能的新基因和新蛋白质提供机会。公共卫生相关性：在人类中，基因的数量估计远高于目前约21，000个基因的估计。由于最近发现基因组普遍转录，我们相信细胞中的大部分RNA也被翻译成蛋白质。如果这是真的，我们的发现将推动许多具有新功能的新基因的发现。

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.