Biomolecular condensates as organizers of mRNA decay in bacteria

尽管没有细胞器，细菌仍表现出一种错综复杂的亚细胞结构。 这是细胞生长、分裂和复制所必需的。一个关键问题是简单的细菌是如何 超越成袋的分子，在空间和时间上组织生理过程 需要维持生命和调节发展吗？已经证明，细菌能够 使用微隔室、曲率感应、类核遮挡和 细胞两极独特的脂类和肽聚糖组成。液相分离液滴， 被称为生物分子凝聚体，在空间上组织的生化途径是无膜的 真核生物中的细胞器包括P小体和应激颗粒。与贾里德合作 Schrader的实验室，我们发现核糖核酸酶RNaseE形成液相分离 细菌核糖核蛋白小体(BR小体)与P小体和应激有相似之处 颗粒。在这个方案中，我们研究了：1)促进RNase E-BR-Body的机制 形成，2)调节BR-小体对信使RNA选择性渗透性的机制 3)核糖核酸酶E支架和生物分子缩合的作用 在信使核糖核酸衰变时。我们对BR小体的研究可能会提供一个具有启发性的初步例子 生物分子缩合物作为细菌内生物化学的中心组织者，并揭示了新的 基因调控的模式。这种对信使核糖核酸衰变的新理解也应该揭示出新的 对管理细菌毒力途径的调控过程的洞察并确定潜在的 破坏BR机体功能的抗生素策略。

Despite the absence of organelles, bacteria exhibit an intricate subcellular organization that is required for cells to grow, divide and replicate. A key question is how do simple bacteria go beyond bags of molecules to spatially and temporally organize physiological processes needed to sustain life and regulate development? It has been shown that bacteria achieve subcellular organization using microcompartments, curvature sensing, nucleoid occlusion, and unique lipid and peptidoglycan composition at the cell poles. Liquid-phase separated droplets, termed biomolecular condensates, spatially organize biochemical pathways as membraneless organelles in eukaryotes including P-bodies and stress granules. In collaboration with Jared Schrader's lab, we discovered that ribonuclease Rnase E forms liquid-phase separated bacterial ribonucleoprotein bodies (BR-bodies) that share similarities with P-bodies and stress granules. In this proposal we investigate: 1) the mechanisms that promote Rnase E BR-body formation, 2) mechanisms that regulate selective permeability of BR-bodies to messenger RNA over non-coding RNAs, and 3) the role of Rnase E scaffolding and biomolecular condensation upon mRNA decay. Our studies of BR-bodies will likely provide an illuminating initial example of biomolecular condensates as central organizers of biochemistry within bacteria, and reveal new modes of genetic regulation. This new understanding of mRNA decay should also reveal new insights into regulatory processes that govern bacterial virulence pathways and identify potential antibiotic strategies that disrupt BR-body functions.