Defining Environmental Influence on RNA Processing

核糖核酸酶通过推动不同物种的RNA周转来调节细胞对环境的反应 RNA代谢途径；然而，我们对连接RNA的分子网络的了解有限 对环境压力的处理阻碍了我们对这些关键反应如何促进细胞的了解 健康和生存。我的研究的长期目标是确定环境是如何加剧 活动性与人类疾病相关的RNA加工因子。线粒体是应激的中枢 适应并在环境变化期间经历RNA加工的动态变化。作为 线粒体是细胞的动力源，为适应压力提供必要的燃料。PNPase发挥作用 在线粒体动态平衡中发挥核心作用，但调节其 功能仍然是一个谜。PNPase外切核糖核酸酶与SUV3解旋酶结合形成 线粒体RNA降解体，它协调线粒体RNA的衰退。PNPase是一种新陈代谢 微调RNA降解体活性的传感器，通过未知的 机制。这一提议的中心假设是，RNA处理在细胞中起着至关重要的作用 对我们的环境做出反应。这个项目的基本原理是揭示分子基础 应激反应RNA加工复合体将提供一个新的框架来理解 环境影响关键的RNA加工事件。这项建议将研究(1)线粒体如何 RNA降解体使RNA周转与细胞的代谢状态同步，以及(2)RNA如何 降解体识别其RNA底物以监测线粒体RNA。为了实现这些目标，一个 多学科课程，包括杂交结构生物学、生物化学、细胞生物学和分子 生物学将被用来理解RNA降解体的调节和功能 对环境压力和刺激的反应。

Ribonucleases modulate the cellular response to our environment by driving RNA turnover across diverse RNA metabolic pathways; yet, our limited understanding of the molecular networks linking RNA processing to environmental stress hinders our knowledge of how these critical responses promote cell fitness and survival. The long-term goal of my research is to define how the environment exacerbates the activity of human disease associated RNA processing factors. Mitochondria are central for stress adaptation and undergo dynamic alterations in RNA processing during environmental changes. As the powerhouse of the cell, the mitochondria supplies the necessary fuel for stress adaptation. PNPase plays a central role in mitochondrial homeostasis, but the underlying molecular mechanism regulating its function remains a mystery. The PNPase exoribonuclease associates with the SUV3 helicase to form the mitochondrial RNA degradosome, which orchestrates mitochondrial RNA decay. PNPase is a metabolic sensor that fine-tunes RNA degradosome activity with the metabolic state of the cell through an unknown mechanism. The central hypothesis of this proposal is that RNA processing plays vital roles in the cellular response to our environment. The rationale for this project is that uncovering the molecular basis for stress-responsive RNA processing complexes will provide a novel framework to understand how the environment impacts critical RNA processing events. This proposal will study (1) How the mitochondrial RNA degradosome syncs RNA turnover with the metabolic state of the cell and (2) How the RNA degradosome recognize its RNA substrates for mitochondrial RNA surveillance. To achieve these goals, a multi-disciplinary program that includes hybrid structural biology, biochemistry, cell biology, and molecular biology will be implemented to understand the regulation and function of the RNA degradosome in response to environmental stress and stimuli.