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The Discovery of Human Peptide Encoding Genes

人类肽编码基因的发现

基本信息

批准号：
8549273
负责人：
Alan Saghatelian
金额：
$ 35.24万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-21 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8549273
关键词：
Acids Amino Acids Bacteria Bioinformatics Biology Cataloging Catalogs Cell Line Cell Nucleus Cell Proliferation Cell physiology Cells Characteristics Disease Functional RNA Gene Expression Profile Gene Expression Regulation Genes Genome Goals Human Human Cell Line Human Genome Immunofluorescence Immunologic Indium Initiator Codon Investigation K562 Cells Knowledge Libraries Liquid Chromatography Metabolism Mitochondria Mitochondrial Proteins Nuclear Nuclear Proteins Open Reading Frames Organelles Peptides Phosphorus 32 Plants Production Protein Family Proteins Proteome RNA Sequences Reporting Role Testing Validation Yeasts base cancer cell cell growth cellular protein p32 fly insight interest leukemia next generation novel novel strategies protein function protein protein interaction research study tandem mass spectrometry two-dimensional

项目摘要

DESCRIPTION (provided by applicant): This application describes a novel approach for the discovery of non-annotated short open reading frame encoded peptides and small proteins (SEPs), a unique class of understudied peptides in the human genome. Application of this approach to a human leukemia cell line revealed the existence of 32 novel human SEPs, the largest number ever reported. Since SEPs are produced from short open reading frames (sORFs) in the genome this discovery also represents the characterization of 32 new human genes. Analysis of the SEP producing sORFs revealed a number of interesting features about mammalian genes,such as the existence of polycistronic genes, the use of non-ATG start codons to produce protein, and the discovery that some "non- coding RNAs" have been mistakenly assigned because they actually encode peptides. Likewise, some of the SEPs have features typically found in proteins, such as the ability to localize to specific subcellular compartments and partake in protein-protein interactions, which indicates that they may serve functional roles in the cell. One of these newly discovered SEPs, for instance, partners in a specific protein-protein interaction with a known regulator of cancer cell proliferation to suggest a potential function for this SEP in cell growth.The discovery of these SEPs are significant because they indicate that genome and proteome are larger than previously anticipated and demonstrate the need for additional investigation of these unique human genes. The goals of this application are to discover, characterize, and explore the biology, including any role in disease, of SEPs.

描述（由申请人提供）：本申请描述了一种用于发现非注释的短开放阅读框编码肽和小蛋白（SEP）的新方法，SEP是人类基因组中一类独特的未充分研究的肽。将这种方法应用于人类白血病细胞系揭示了32种新的人类SEP的存在，这是有史以来报道的最大数量。由于SEP是由基因组中的短开放阅读框（sORF）产生的，因此这一发现也代表了32个新的人类基因的特征。对产生sORF的SEP的分析揭示了许多关于哺乳动物基因的有趣特征，例如多顺反子基因的存在，使用非ATG起始密码子来产生蛋白质，以及发现一些“非编码RNA”被错误地分配，因为它们实际上编码肽。同样，一些SEP具有通常在蛋白质中发现的特征，例如定位于特定亚细胞区室并参与蛋白质-蛋白质相互作用的能力，这表明它们可能在细胞中发挥功能作用。例如，这些新发现的SEP之一，与已知的癌细胞增殖调节因子进行特定的蛋白质-蛋白质相互作用，表明该SEP在细胞生长中的潜在功能。这些SEP的发现具有重要意义，因为它们表明基因组和蛋白质组比之前预期的要大，并表明需要对这些独特的人类基因进行额外的研究。该应用程序的目标是发现，表征和探索SEP的生物学，包括在疾病中的任何作用。