Biomolecular condensates as organizers of mRNA decay in bacteria

生物分子凝聚体作为细菌 mRNA 衰变的组织者

基本信息

批准号：
10376044
负责人：
William Seth Childers
金额：
$ 30.82万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-21 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10376044
关键词：
Alphaproteobacteria Antibiotics Bacteria Bacterial Genes Behavior Binding Biochemical Pathway Biochemistry Biological Assay Brucella abortus C-terminal Cattle Caulobacter crescentus Cell division Cell physiology Cells Chronic Granulomatous Disease Collaborations Crowding Cytoplasmic Granules Data Development Disease Eukaryota Exhibits Exonuclease Gene Expression Regulation Genetic Goals In Vitro Knowledge Learning Life Lipids Liquid substance Mammalian Cell Messenger RNA Organelles Pathogenesis Pathway interactions Peptidoglycan Permeability Phase Physical condensation Physiological Physiological Processes Plants Process Proteins RNA RNA Decay RNA Degradation Reagent Regulation Rhizobium radiobacter Ribonucleases Ribonucleoproteins Role Sodium Chloride Stress Structure Testing Untranslated RNA Virulence Work base enzyme activity enzyme pathway experimental study fitness in vivo inhibitor insight mRNA Decay mRNA Transcript Degradation pathogen ribonuclease E scaffold self assembly stress granule success

项目摘要

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.

尽管没有细胞器，但细菌表现出复杂的亚细胞组织细胞生长，分裂和复制是必需的。一个关键的问题是如何简单细菌超越分子袋，在空间和时间上组织生理过程需要维持生命并规范发展？已经表明细菌达到了使用微校区，曲率感应，核苷闭塞和亚细胞组织细胞杆处的独特脂质和肽聚糖组成。液相分离的液滴，称为生物分子冷凝物，在空间上组织生化途径为无膜真核生物中的细胞器，包括P体和应力颗粒。与Jared合作 Schrader的实验室，我们发现核糖核酸酶RNase E形成液相分离细菌核糖核蛋白体（BR体）与P-Bodies和压力有相似之处颗粒。在此提案中，我们研究：1）促进RNase E BR体型的机制形成，2）调节BR体型对信使RNA的选择性渗透性的机制在非编码RNA和3）RNase E支架和生物分子冷凝的作用在mRNA衰变上。我们对BR体型的研究可能会提供一个启发性的初始例子生物分子冷凝物是细菌内生物化学的中央组织者，并揭示了新的遗传调节模式。对mRNA衰变的新理解也应该揭示新的对控制细菌毒力途径的调节过程的见解并确定潜力破坏BR体功能的抗生素策略。