R-loops: from molecular principles to their roles in human disease

R 环：从分子原理到它们在人类疾病中的作用

• 批准号: MR/X020487/1
• 负责人: Natalia Gromak
• 金额: $ 295.04万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX020487%2F1
• 关键词: loops; molecular; principles; their; roles

DNA encodes the instructions necessary for our cells to function. In order to read DNA's instructions, cells must first convert them into the RNA code, in a process called transcription. During transcription, newly made RNA can bind to the original DNA strand, forming structures called R-loops. R-loops are formed in all living organisms and are essential for many cellular processes. However, uncontrolled accumulation of R-loops can lead to severe human diseases such as cancer and neurodegeneration. Therefore, it is important to understand how R-loops are regulated. We will use state-of-the-art technology to study factors that control R-loop behavior in healthy cells. We will identify the mechanisms of their action, characterize their cellular targets and reveal their complex relationship with each other. This information will shed light on how R-loops contribute to human neurodegenerative diseases, and potentially identify new therapeutic targets.

DNA编码我们的细胞运作所必需的指令。为了阅读DNA的指令，细胞必须首先将它们转换成RNA代码，这一过程被称为转录。在转录过程中，新合成的RNA可以与原始DNA链结合，形成称为R-环的结构。R环存在于所有生物体中，对许多细胞过程都是必不可少的。然而，R环的不受控制的积累可能会导致严重的人类疾病，如癌症和神经退化。因此，重要的是要了解R-环是如何调节的。我们将使用最先进的技术来研究控制健康细胞中R环行为的因素。我们将确定它们的作用机制，表征它们的细胞靶标，并揭示它们彼此之间的复杂关系。这些信息将阐明R环如何导致人类神经退行性疾病，并可能确定新的治疗靶点。