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

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，我们已经表明，与当前的模型相反，RNase E可以直接测量多个站点，而不受5‘端系绳的限制。我们还概述了潜在的机制。这项具有重要影响的工作由BBSRC资助，并在他们的网站上展示。目的：除了以上，我们的发现可能会使我们对基因调控的理解发生翻天覆地的变化。我们已经发现，RNaseE超越了它切割的RNA，并几乎与它遇到的任何东西结合。这个项目的主要目标是确定RNase E与5‘非翻译区(UTRs)的结合是否代表了在大肠杆菌中调节翻译的主要途径。其具体目的是(1)证实RNaseE以高亲和力与许多5‘UTRs结合，(2)证实30S核糖体亚基的结合可以被RNaseE击败，以及(3)确定RNaseE结合对翻译的整体影响。以前从未有人提出过RNaseE，甚至任何其他核糖核酸酶，可以通过竞争优势与5‘UTRs结合来调节翻译。此外，第一次切割前mRNAs的失活可以防止部分降解的转录本的无效翻译，甚至可能是有害的翻译。我们最新的直接进入论文是作为一篇“突破”文章发表的，并被放在了封面上。及时性：拟议的项目不仅基于一系列强有力的出版物以及最近出人意料和史无前例的发现，而且符合合成生物学和新抗生素开发的主要倡议。

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.