The Discovery of Human Peptide Encoding Genes

描述（由申请人提供）：本申请描述了一种用于发现非注释短开放阅读框编码肽和小蛋白（sep）的新方法，这是人类基因组中一类独特的未被研究的肽。将这种方法应用于人类白血病细胞系，发现了32个新的人类sep，这是迄今为止报道的最多的。由于sep是由基因组中的短开放阅读框（sorf）产生的，这一发现也代表了32个新的人类基因的特征。对产生SEP的sorf的分析揭示了许多关于哺乳动物基因的有趣特征，如多顺反子基因的存在，使用非atg启动密码子产生蛋白质，以及发现一些“非编码rna”被错误分配，因为它们实际上编码肽。同样，一些sep具有在蛋白质中发现的典型特征，例如定位到特定亚细胞区室和参与蛋白质-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，其中一种新发现的sep，在一种特定的蛋白质中与一种已知的癌细胞增殖调节因子相互作用

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.