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.

项目负责人/主要研究者（最后，第一，中间）：Bartel，大卫P。 标题：转录后基因调控 项目概要： 许多真核生物基因调控发生在转录后，通过差异mRNA稳定性和/或 翻译效率本提案的研究旨在回答两个基本问题， 转录后基因控制的相关领域：microRNA和mRNA的非编码特征。 微小RNA（microRNAs，miRNAs）是与mRNA配对以指导其去稳定和翻译的~22-nt RNA。 镇压在人类中已经发现了600多个miRNA基因，因为大多数人类基因 作为miRNAs的保守靶点，miRNAs在哺乳动物中发挥重要作用也就不足为奇了。 发育和生理以及人类疾病，包括病毒感染和癌症。分子， 计算和结构方法将用于确定1）miRNA靶向的生物化学基础， 识别和改进的方法来预测最压抑的目标，2）的原因，一些 miRNAs比其他的更容易指导结合的mRNA靶的切割，和3）其机制和 生物化学途径的生物学范围，细胞利用该途径靶向特定的miRNA进行降解。结果 这些研究有望增强对这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 miRNAs在人类疾病中的作用 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。分子和计算方法将用于 确定1）酵母中切除内含子稳定化的分子基础，2）G-四链体的机制 在细胞中展开，以及3）为什么较长的poly（A）尾增强后生动物卵母细胞和早期胚胎中的翻译， 以及为什么随着胚胎的发育，尾巴长度和翻译效率之间的关系消失了。 这些结果有望为酵母细胞的生长调控和翻译后基因的研究提供基础 后生动物发育的调控，对人类生育力、发育缺陷或 其它疾病