Identity and Functions of Selenoprotein Genes

硒蛋白基因的身份和功能

• 批准号: 7252435
• 负责人: Vadim N. Gladyshev
• 金额: $ 27.64万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7252435
• 关键词: Active Sites; Address; Alternative Splicing; Amino Acids; Animals; Binding; Bioinformatics; Biological; Biological Models; Biology; Cell Culture System; Code; Codon Nucleotides; Coupled; Cysteine; DNA Insertion Elements; Data; Databases; Dietary Selenium; Disulfides; Evolution; Family; Foundations; Funding; Gene Expression; Genes; Genetic Code; Genetic Polymorphism; Genome; Health; Health Benefit; Homologous Gene; Human Biology; Human Genome; IS Elements; Immune system; In Vitro; Mediating; Membrane; Methods; Neighborhoods; Organism; Oxidation-Reduction; Phylogenetic Analysis; Procedures; Process; Proteins; RNA; Reproduction; Research Personnel; Role; Saccharomyces cerevisiae; Selenium; Selenocysteine; Sequence Homologs; Signal Transduction; Structure; Surveys; System; Testing; Tissues; Trace Elements; base; cancer prevention; fusion gene; genome sequencing; improved; insight; interest; male; novel; programs; response; selenoprotein; tool; transposon/insertion element

DESCRIPTION (provided by applicant): Selenium is an essential trace element with significant health benefits. It has potent cancer prevention activity and roles in the immune system, male reproduction, and many other biological systems and processes. Most of these selenium's effects are mediated by selenocysteine (Sec)-containing proteins. However, information about these proteins is scarce. Sec is known as the 21st amino acid in the genetic code and is co-translationally inserted into proteins in response to UGA codon. Identification and functional analysis of selenoproteins are challenging. Because UGA codon normally serves as a stop signal, selenoprotein genes are misannotated or completely missed in genome annotations. In the previous funding cycle, we developed bioinformatics tools that allow identification of selenoprotein genes by searching for conserved RNA structures, called Sec insertion sequence (SECIS) elements, and identifying selenocysteine/cysteine-containing protein pairs of homologs. By using these tools, we were able to characterize selenoproteomes (entire sets of selenoproteins in an organism) encoded in many completely sequenced genomes, including the human genome. We also provided experimental evidence for the occurrence of newly identified selenoproteins and determined functions of several selenoproteins using computational and experimental approaches. The major focus of the current application is to functionally characterize mammalian selenoproteins. The proposed study will be guided by three specific aims: 1) identification of selenoprotein genes in completely sequenced genomes and genome survey projects, demonstration of their occurrence, and analyses of polymorphisms; 2) functional characterization of newly identified mammalian selenoproteins with the focus on their interaction partners; and 3) analysis of selenoprotein functions using model systems. The PI's previous data establish that it is feasible to identify all or almost all selenoprotein genes encoded in completely sequenced genomes and to functionally characterize selenoproteins of particular interest. The results generated should help explain many biological and biomedical effects of dietary selenium, provide insights into evolution of selenocysteine, and identify proteins with redox function.

描述（由申请人提供）：硒是一种重要的微量元素，具有显着的健康益处。它具有有效的癌症预防活性，并在免疫系统、男性生殖以及许多其他生物系统和过程中发挥作用。硒的大部分作用是由含硒半胱氨酸 (Sec) 的蛋白质介导的。然而，有关这些蛋白质的信息很少。 Sec 被称为遗传密码中的第 21 个氨基酸，响应 UGA 密码子共翻译插入蛋白质中。硒蛋白的鉴定和功能分析具有挑战性。由于 UGA 密码子通常充当终止信号，因此硒蛋白基因在基因组注释中被错误注释或完全遗漏。在上一个资助周期中，我们开发了生物信息学工具，通过搜索保守的 RNA 结构（称为 Sec 插入序列 (SECIS) 元素）并识别含硒半胱氨酸/半胱氨酸同源蛋白对来识别硒蛋白基因。通过使用这些工具，我们能够表征许多完整测序的基因组（包括人类基因组）中编码的硒蛋白质组（生物体中的整套硒蛋白质）。我们还为新发现的硒蛋白的出现提供了实验证据，并使用计算和实验方法确定了几种硒蛋白的功能。当前应用的主要焦点是哺乳动物硒蛋白的功能表征。拟议的研究将遵循三个具体目标：1）在完全测序的基因组和基因组调查项目中鉴定硒蛋白基因，证明其发生并分析多态性； 2）新鉴定的哺乳动物硒蛋白的功能表征，重点关注其相互作用伙伴； 3) 使用模型系统分析硒蛋白功能。 PI 之前的数据表明，鉴定完全测序的基因组中编码的所有或几乎所有硒蛋白基因以及对特别感兴趣的硒蛋白进行功能表征是可行的。产生的结果应有助于解释膳食硒的许多生物学和生物医学效应，提供对硒代半胱氨酸进化的见解，并识别具有氧化还原功能的蛋白质。