Post-transcriptional gene regulation

项目主任/首席调查员(最后、第一、中间)：Bartel，David P. 标题：转录后基因调控 项目总结： 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 翻译效率。对这一提议的研究试图在两个方面回答基本问题 转录后基因控制的相关领域：microRNA和mRNAs的非编码特征。 MicroRNAs(MiRNAs)是与mRNAs配对的~22-nt RNAs，指导其失稳和翻译 压抑。已在人类中鉴定出600多个miRNA基因，因为大多数人类基因 都是miRNAs的保守靶标，因此miRNAs在哺乳动物中发挥重要作用就不足为奇了。 发展和生理，以及人类疾病，包括病毒感染和癌症。分子， 将使用计算和结构方法来确定1)miRNA-靶的生物化学基础 最受抑制目标的识别和改进的预测方法；2)部分原因 MiRNAs更容易指导结合的mRNA靶标的切片，以及3)机制和 生物化学途径的生物学范围，细胞用来针对特定的miRNAs进行降解。结果 这些研究有望加强对这一重要类别基因的基本了解-- 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 人类疾病中的miRNAs。 信使核糖核酸的非编码特征，包括切除的内含子、稳定折叠的信使核糖核酸结构和信使核糖核酸 Poly(A)尾巴，可以调节调节现象。分子和计算方法将被用于 确定1)酵母中外切内含子稳定的分子基础，2)G-四链体的机制 在细胞中展开，以及3)为什么较长的聚(A)尾巴在后生动物卵母细胞和早期胚胎中增强翻译， 以及为什么随着胚胎的发育，尾巴长度和翻译效率之间的这种关系消失了。 这些结果有望为酵母和翻译后基因的生长控制提供基本的见解。 后生动物发育的调节，对人类生育力、发育缺陷或 其他疾病。

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.