Impact of Non-canonical Decoding on the Proteome

非规范解码对蛋白质组的影响

• 批准号: 7915166
• 负责人: Joseph A Loo
• 金额: $ 30.49万
• 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/7915166
• 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; 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 翻译的本地重编程，以丢弃标准翻译规则并以非规范方式解码。这种刺激过程的产物，即包含阅读框移位的蛋白质、绕过的核苷酸片段和/或意外的氨基酸，已在所有 3 个结构域中观察到，并且已知对基因表达的转录后调节有重要贡献。我们的假设是，重新编码和错误编码的蛋白质比之前预期的更重要，但它们始终被高通量蛋白质组学方法所忽视，这些方法将蛋白质组视为基因组的镜子。我们相信，改变的蛋白质组工作流程可以揭示体内重新编码和错误编码的蛋白质，并且这些方法可以为一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疗法的开发，并且可以对某些仅因同义多态性而不同的基因产物所观察到的异常活性差异提出解释。他们还可能提出了伪信使 RNA 的功能。 B. 项目叙述 该提案描述了一种检查合成生命必需成分的替代途径的重要性的方法。如果发现该途径比之前预期的更重要，它将提示某些疾病的原因和潜在的治疗方法。