Impact of Non-canonical Decoding on the Proteome

非规范解码对蛋白质组的影响

• 批准号: 7515171
• 负责人: Joseph A Loo
• 金额: $ 30.8万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7515171
• 关键词: Amino Acid Sequence; Amino Acids; Bypass; Disease; Gene Expression; Genetic Polymorphism; Genetic Translation; Genome; Hereditary Disease; Life; Messenger RNA; Methods; Microbiology; Nucleotides; Pathway interactions; Post-Transcriptional Regulation; Process; Proteins; Proteome; Proteomics; Reading Frames; Research; Standards of Weights and Measures; Translations; abstracting; in vivo; therapy development

DESCRIPTION (provided by applicant): A. Project Summary/Abstract Recoding describes the local reprogramming of mRNA translation to discard standard translational rules and decode non-canonically. The products of this stimulated process, proteins incorporating shifts in reading frame, bypassed nucleotide segments, and/or unexpected amino acids have been observed in all 3 domains and are known to contribute importantly to post-transcriptional regulation of gene expression. Our hypothesis is that recoded and miscoded proteins are more important than previously anticipated, but that they are consistently overlooked by high-throughput proteomic methods that regard the proteome as a mirror of the genome. We believe that an altered proteomic workflow can reveal proteins recoded and miscoded in vivo, and that these methods can provide amino acid sequences for some of the recoded products. If successful, these efforts can potentially impact research in protein translation, microbiology, and proteomics. They can impact the development of therapies for genetic diseases, and can suggest explanations for the unusual activity differences observed for some gene products differing only by a synonymous polymorphism. They may also suggest a function for pseudo-messenger RNA. B. Project Narrative This proposal describes a method to examine the importance of an alternate pathway for synthesizing essential components of life. Should the pathway be found to be more important than previously anticipated, it will suggest causes and potential therapies for some disorders.

描述（由申请人提供）：A。项目摘要/摘要重新编码描述了mRNA翻译的局部重编程以丢弃标准翻译规则，并非传统地解码。在所有3个结构域中都观察到了这种刺激过程的产物，蛋白质，在阅读框架中掺入偏移，绕过的核苷酸段和/或意外的氨基酸，并且已知对基因表达的转录后调节有重要作用。我们的假设是，经过重新编码的蛋白质比以前预期的更重要，但是将它们视为基因组的镜像的高通量蛋白质组学方法始终被忽视。我们认为，改变的蛋白质组学工作流可以揭示体内重新编码和编码的蛋白质，并且这些方法可以为某些重新编码的产物提供氨基酸序列。如果成功，这些努力可能会影响蛋白质翻译，微生物学和蛋白质组学的研究。它们可以影响遗传疾病的疗法的发展，并可以提出对某些基因产物观察到的异常活性差异的解释，而某些仅由同义多态性不同。他们也可能建议使用伪符号RNA的功能。 B.项目叙述该建议描述了一种研究替代途径综合生活基本组成部分的重要性的方法。如果发现该途径比以前预期的更为重要，那么它将提出某些疾病的原因和潜在疗法。