Is the capture of RNA by RNase E and not its cleavage the major initiator of mRNA turnover?

RNase E 对 RNA 的捕获而不是其切割是 mRNA 周转的主要引发剂吗？

• 批准号: 1647923
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1647923
• 关键词: capture; RNA; RNase; its; cleavage

E. coli RNase E is a major regulator of gene expression and homologues are found in many bacteria and plant plastids. In a series of landmark papers published this year, we have shown that contrary to current models RNase E can survey multiple sites directly without being constrained by 5'-end tethering. We have also outlined the underlying mechanism. This work, which has important ramifications, was funded by the BBSRC and featured on their website.Objectives: In addition to the above, we have made a finding that may produce a seismic shift in our understanding of gene regulation. We have found that RNase E reaches beyond the RNA it cleaves and binds to virtually any it encounters. The broad objective of this project is to establish whether the binding of 5' untranslated regions (UTRs) by RNase E represents a major route by which translation is regulated in E. coli. The specific aims are to (1) confirm that RNase E binds to many 5' UTRs with high affinity, (2) establish that binding of 30S ribosomal subunits can be outcompeted by RNase E, and (3) determine the overall influence of RNase E binding on translation.Novelty: The hypothesis is novel. Never before has it been proposed that RNase E, or indeed any other ribonuclease, can regulate translation by outcompeting ribosomes for binding to 5' UTRs. Moreover, the inactivation of mRNAs before the first cleavage could prevent the futile and perhaps deleterious translation of partially degraded transcripts. Our most recent direct entry paper was published as a "Breakthrough" article and was given the front cover. Timeliness: The proposed project not only comes on the back of a series of strong publications plus recent findings that were unexpected and unprecedented, it fits with major initiatives in synthetic biology and the development of new antibiotics.

E.大肠杆菌核糖核酸酶E是基因表达的主要调节因子，在许多细菌和植物质体中发现了同源物。在今年发表的一系列具有里程碑意义的论文中，我们已经证明，与当前的模型相反，RNase E可以直接测量多个站点，而不受5 '端拴系的限制。我们还概述了基本机制。这项工作，这有重要的影响，是由BBSRC资助，并在他们的website.Objectives特色：除了上述，我们已经取得了一项发现，可能会产生一个地震转变，在我们的理解基因调控。我们发现RNase E的作用范围超出了它所切割的RNA，并与它所遇到的几乎任何RNA结合。本项目的主要目的是确定RNase E对5'非翻译区（UTR）的结合是否代表了E.杆菌具体的目的是（1）证实RNase E以高亲和力结合许多5'UTR，（2）建立30 S核糖体亚基的结合可以被RNase E竞争，和（3）确定RNase E结合对翻译的总体影响。新奇：该假设是新颖的。以前从未有人提出RNase E或任何其他核糖核酸酶可以通过竞争核糖体与5'UTR结合来调节翻译。此外，在第一次切割之前mRNA的失活可以防止部分降解的转录物的无效和可能有害的翻译。我们最近的直接进入论文发表为“突破”文章，并获得了封面。时间：该项目不仅是在一系列强有力的出版物以及最近出乎意料和前所未有的发现的基础上提出的，而且符合合成生物学和新抗生素开发的重大举措。