Defining Environmental Influence on RNA Processing

定义环境对 RNA 加工的影响

• 批准号: 10620138
• 负责人: Monica Pillon
• 金额: $ 24.9万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10620138
• 关键词: Defining; Environmental; Influence; RNA; Processing

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.

核糖核酸酶通过驱动RNA在不同环境中的周转来调节细胞对环境的反应。 然而，我们对连接RNA的分子网络的有限理解 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生长的认识。 健身和生存。我的研究的长期目标是确定环境如何加剧 人类疾病相关RNA加工因子的活性。线粒体是压力的核心 在环境变化过程中，RNA的加工过程会发生动态变化。为 线粒体是细胞的发电站，为压力适应提供必要的燃料。Pennsylvania戏剧 线粒体内稳态的核心作用，但潜在的分子机制调节其 功能仍然是一个谜。PND3核糖核酸外切酶与SUV 3解旋酶结合以形成PND3。 线粒体RNA降解体，其协调线粒体RNA降解。PNTR是一种代谢性 传感器，通过未知的细胞代谢状态微调RNA降解体活性， 机制这个提议的中心假设是RNA加工在细胞内的转录过程中起着至关重要的作用。 对我们环境的回应。这个项目的基本原理是，揭示的分子基础， 应激反应的RNA加工复合物将提供一个新的框架，以了解如何 环境影响关键的RNA加工事件。本文将研究（1）线粒体如何在 RNA降解体使RNA周转与细胞的代谢状态同步，以及（2）RNA降解体如何使RNA周转与细胞的代谢状态同步。 降解体识别其RNA底物用于线粒体RNA监视。为了实现这些目标，A 一个多学科的计划，包括混合结构生物学，生物化学，细胞生物学，和分子 生物学将被实施，以了解RNA降解体的调节和功能， 对环境压力和刺激的反应。