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

大肠杆菌 RNase E 是基因表达的主要调节因子，在许多细菌和植物质体中都发现了同源物。在今年发表的一系列具有里程碑意义的论文中，我们表明，与当前模型相反，RNase E 可以直接调查多个位点，而不受 5' 端束缚的限制。我们还概述了基本机制。这项具有重要影响的工作由 BBSRC 资助，并在其网站上进行了专题报道。 目标：除了上述内容之外，我们还发现了一项可能会彻底改变我们对基因调控的理解的发现。我们发现 RNase E 的作用范围超出了它所切割的 RNA 范围，并且几乎与它遇到的任何 RNA 结合。该项目的主要目标是确定 RNase E 与 5' 非翻译区 (UTR) 的结合是否代表大肠杆菌中调节翻译的主要途径。具体目标是 (1) 确认 RNase E 以高亲和力与许多 5' UTR 结合，(2) 确定 30S 核糖体亚基的结合可以被 RNase E 竞争，以及 (3) 确定 RNase E 结合对翻译的总体影响。 新颖性：该假设是新颖的。以前从未有人提出过 RNase E 或任何其他核糖核酸酶可以通过竞争核糖体与 5' UTR 的结合来调节翻译。此外，在第一次切割之前使 mRNA 失活可以防止部分降解的转录本无效且可能有害的翻译。我们最近的直接进入论文作为“突破”文章发表，并被授予封面。及时性：拟议的项目不仅是在一系列强有力的出版物和最近出乎意料且前所未有的发现的基础上提出的，它符合合成生物学和新抗生素开发的重大举措。

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.