Post-transcriptional gene regulation

转录后基因调控

• 批准号: 10207005
• 负责人: DAVID P BARTEL
• 金额: $ 73.43万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10207005
• 关键词: Area; Biochemical; Biochemical Pathway; Biological; Cells; Congenital Abnormality; Defect; Development; Disease; Embryo; Fertility; G-Quartets; Gene Expression Regulation; Genes; Genetic Transcription; Growth; Human; Introns; Length; Malignant Neoplasms; Mediating; Messenger RNA; Methods; MicroRNAs; Molecular; Molecular Computations; Oocytes; Physiology; Play; Poly(A) Tail; Post-Transcriptional Regulation; Principal Investigator; Process; Proteins; RNA; Regulator Genes; Research Proposals; Resources; Role; Slice; Structure; Tail; Translational Repression; Translations; Untranslated RNA; Viral Cancer; Virus Diseases; Yeasts; experimental study; gene function; human disease; improved; insight; mRNA Stability; novel therapeutics; programs

Program Director/Principal Investigator (Last, First, Middle): Bartel, David P. TITLE: Post-transcriptional gene regulation PROJECT SUMMARY: Much of eukaryotic gene regulation occurs post-transcriptionally, through differential mRNA stability and/or translational efficiency. The research of this proposal seeks to answer fundamental questions within two interrelated areas of post-transcriptional gene control: microRNAs and non-coding features of mRNAs. MicroRNAs (miRNAs) are ~22-nt RNAs that pair to mRNAs to direct their destabilization and translational repression. More than 600 miRNA genes have been identified in humans, and because most human genes are conserved targets of miRNAs, it is no surprise that miRNAs play important roles in mammalian development and physiology, as well as human diseases, including viral infections and cancers. Molecular, computational, and structural approaches will be used to determine 1) the biochemical basis of miRNA–target recognition and improved methods for predicting the most repressed targets, 2) the reasons that some miRNAs direct the slicing of bound mRNA targets much more readily than others, and 3) the mechanism and the biological scope of a biochemical pathway that cells use to target specific miRNAs for degradation. Results of these studies are expected to enhance the fundamental understanding of this important class of gene- regulatory molecules and provide resources helpful for many biologists, including those studying the roles of miRNAs in human diseases. The noncoding features of mRNAs, including excised introns, stably folded mRNA structures, and mRNA poly(A) tails, can mediate regulatory phenomena. Molecular and computational approaches will be used to determine 1) the molecular basis of excised-intron stabilization in yeast, 2) the mechanism of G-quadruplex unfolding in cells, and 3) why longer poly(A) tails enhance translation in metazoan oocytes and early embryos, and why this relationship between tail length and translation efficiency disappears as the embryo develops. Results are expected to provide fundamental insight into growth control in yeast and post-translational gene regulation in metazoan development, with potential implications for human fertility, developmental defects, or other diseases.

项目总监/首席研究员（最后、第一、中间）：Bartel, David P. 标题：转录后基因调控 项目概要： 许多真核基因调控发生在转录后，通过不同的 mRNA 稳定性和/或 该提案的研究旨在回答两个内的基本问题。 转录后基因控制的相关领域：microRNA 和 mRNA 的非编码特征。 MicroRNA (miRNA) 是 ~22-nt RNA，与 mRNA 配对以指导其不稳定和翻译 人类中已鉴定出 600 多个 miRNA 基因，并且大多数人类基因都受到抑制。 是 miRNA 的保守靶标，因此 miRNA 在哺乳动物中发挥重要作用也就不足为奇了。 发育和生理学，以及人类疾病，包括病毒感染和癌症。 将使用计算和结构方法来确定 1) miRNA 靶标的生化基础 识别和改进的方法来预测最受压抑的目标，2）一些原因 miRNA 比其他的 miRNA 更容易指导结合的 mRNA 靶标的切片，3）机制和 细胞用于靶向特定 miRNA 进行降解的生化途径的生物学范围。 这些研究有望增强对这一类重要基因的基本理解 调节分子并为许多生物学家提供有用的资源，包括那些研究调节分子作用的生物学家 人类疾病中的 miRNA。 mRNA 的非编码特征，包括切除的内含子、稳定折叠的 mRNA 结构和 mRNA 聚（A）尾，可以介导调节现象，将用于调节现象。 确定 1) 酵母中切除内含子稳定的分子基础，2) G-四链体的机制 3) 为什么较长的聚腺苷酸尾会增强后生动物卵母细胞和早期胚胎中的翻译， 以及为什么尾长和翻译效率之间的关系随着胚胎发育而消失。 预计结果将为酵母和翻译后基因的生长控制提供基本见解 后生动物发育的调节，对人类生育能力、发育缺陷或具有潜在影响 其他疾病。