Physiologic state modulation by conditional translational complexes

基因表达的过程，包括转录和翻译，与细胞生理学密切相关，并由地球上的所有生物体进行。然而，翻译过程及其对细胞生理的影响通常被认为是从属于转录调控和翻译后信号转导。尽管事实上转录和信号传导都依赖于蛋白质，因此也依赖于翻译，但这一概念仍然存在。该项目旨在确定基因表达和生理学中被忽视的普遍方面。 该项目将测试一种新的想法，即在特定环境条件下所需的蛋白质在暴露于这种条件下时会优先翻译。 拟议中的研究可能会揭示一种新的基因调控分子机制，并将大大推进我们对翻译在控制无数生命过程中的统一核心作用的理解。 此外，该项目将有助于培训K-12学生和教师，以及高中科学课程的开发。 拟议的研究将解决翻译系统的组件的功能多样性及其转录产生的模块化表达是否调节生物体中的大规模生理状态转变。潜在的假设是，环境依赖性的生理细胞状态是由具有可变亚基组成的不同核糖体复合物的条件性生产、组装和活性产生的。这一假说是基于转基因多样性生物体的基因调控网络内的翻译机制基因的有趣组织。具体而言，核糖体亚基和其他翻译系统蛋白质作为多个不同但重叠的模块在环境变化中具有不相关的表达模式而被有条件地共调节。拟议的研究将试图观察某些核糖体亚基的条件关联，以及这种关联是否指导翻译复合物优先翻译特定环境相关生理状态的转录本编码功能。核糖体复合物的蛋白质（使用SWATH质谱法）和mRNA（具有RNA-seq）组成将在环境变化（例如，需氧到厌氧），其影响大的生理状态转变。此外，拟议的研究将可预测地操纵每个生物体的生理状态，通过工程环境响应调节或敲除条件核糖体亚基。特定条件表达的核糖体亚基的调节改变应该表现出相对于环境转变的不适当的生理状态转变。将通过使用来自生命三个领域的模式微生物进行研究来评估假设的普遍性- H。salinarum（archaeon）、盐生古菌E. coli（细菌）和S.酿酒酵母（真核生物）。这些拟议的活动将证明是否可变的翻译复合物驱动环境依赖性的生理转变。

The process of gene expression, encompassing transcription and translation, is closely interconnected with cellular physiology, and is carried out by all organisms on Earth. Yet, the process of translation and its impact on cellular physiology is generally thought to be subordinate to transcriptional regulation and post-translational signaling. This notion continues despite the fact that both transcription and signaling depend on proteins, and hence on translation. This project seeks to identify a universal aspect of gene expression and physiology that has been overlooked. This project will test the novel idea that proteins needed under particular environmental conditions are preferentially translated when exposed to such conditions. The proposed studies may uncover a new molecular mechanism for gene regulation and will greatly advance our understanding of the unifying, central role of translation in controlling a myriad life processes. In addition, the project will contribute to training of K-12 students and teachers, and high school science curriculum development. The proposed research will address whether functional diversity of components of the translation system and their transcriptionally generated modular expression regulate large-scale physiological state transitions in organisms. The underlying hypothesis is that environment-dependent physiological cell states are generated by the conditional production, assembly, and activity of distinct ribosomal complexes with variable subunit compositions. This hypothesis is based on the intriguing organization of translational machinery genes within gene regulatory networks of phylogenetically diverse organisms. Specifically, ribosomal subunits and other translation system proteins are conditionally co-regulated as multiple distinct, yet overlapping modules with un-correlated expression patterns across environmental shifts. The proposed research will attempt to observe conditional association of certain ribosomal subunits, and whether this association directs the translation complex to preferentially translate transcripts encoding functions for a particular environment-relevant physiological state. Protein (using SWATH mass spectrometry) and mRNA (with RNA-seq) compositions of ribosomal complexes will be characterized across environmental shifts (e.g., aerobic to anaerobic) that effect large physiological state transitions. Additionally, the proposed research will predictably manipulate the physiological state of each organism by engineering environment-responsive regulation or knock outs of conditional ribosomal subunits. Altered regulation of specific conditionally expressed ribosomal subunits should manifest an inappropriate physiological state transition relative to the environmental shift. Generality of the hypothesis will be assessed by performing studies using model microorganisms from the three domains of life - H. salinarum (archaeon), E. coli (bacterium), and S. cerevisiae (eukaryote). These proposed activities will demonstrate whether variable translation complexes drive environment-dependent physiological transitions.