Characterizing functional translation in putative 'noncoding' regions of a genome

表征基因组假定“非编码”区域的功能翻译

• 批准号: 10224773
• 负责人: Zhe Ji
• 金额: $ 39.88万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10224773
• 关键词: 5' Untranslated Regions; Automobile Driving; Biological; Biological Process; Cell Proliferation; Cells; Computational algorithm; Coupling; Data; Degradation Pathway; Development; Disease; Disease Progression; Elements; Eukaryota; Evolution; Genetic study; Genome; Genomic approach; Light; Mediating; Metabolism; Modeling; Molecular; Normal Range; Open Reading Frames; Other Genetics; Peptides; Pseudogenes; RNA; RNA Stability; Research; Role; Translating; Translations; Untranslated RNA; Work; frontier; insight; novel; ribosome profiling

ABSTRACT It is fundamentally important to understand how functional information is encoded by a genome. Characterizing these functional elements can bring novel mechanistic insights into biological processes ranging from normal development to disease progression. I developed a computational algorithm to analyze ribosome profiling data, and unexpectedly revealed thousands of short open reading frames (sORFs) encoded by putative ‘noncoding’ regions, including lncRNAs, pseudogenes, and 5’UTRs. Some of the sORFs are conserved across species, suggesting biological importance. My results together with several other genetic studies in model species have opened up a research frontier to study the biological roles of sORFs encoded in a genome. Here I propose to use integrated computational and experimental genomics approaches to systematically characterize biological functions of sORFs. First, we will study basic principles driving sORF conservation and expression across eukaryotes. Second, we will study the stability and degradation pathways of sORF-encoded micropeptides. Third, we will examine the importance of sORFs for regulating cell proliferation. Finally, we will study the functional roles of sORF translation in regulating RNA stability. Taken together, our study will shed light on the functional characterization of the newly identified translated regions in a genome and provide novel insights into the interplay between RNA translation and genome evolution. Our findings will have far-reaching implications for the molecular understanding of translational control and peptide functions underlying development and diseases.

抽象的 从根本上了解如何由基因组编码功能信息。特征 这些功能元素可以将新型的机械见解带入从正常的生物过程中 发展为疾病进展。我开发了一种计算算法来分析核糖体分析数据， 出乎意料地揭示了成千上万个用假定的“非编码”编码的简短开放式阅读框（SORF） 包括LNCRNA，假基因和5'Utrs的区域。一些sorf在各种物种之间保守， 提出生物学重要性。我的结果以及模型物种中的其他几项遗传研究具有 打开了研究边界，研究了基因组中编码的SORF的生物学作用。我在这里建议 使用集成的计算和实验基因组学方法系统地表征生物学 Sorfs的功能。首先，我们将研究推动Sorf保护和表达的基本原则 真核生物。其次，我们将研究SORF编码的微肽的稳定性和降解途径。第三， 我们将研究SORFS确定细胞增殖的重要性。最后，我们将研究功能 Sorf翻译在调节RNA稳定性中的作用。综上所述，我们的研究将阐明功能 对基因组中新鉴定的翻译区域的表征，并提供了新的见解 RNA翻译与基因组进化之间的相互作用。我们的发现将对 分子对转化控制和肽功能的分子理解和疾病的基础。