Deciphering a novel interplay between RNA and chromatin

破译RNA和染色质之间的新相互作用

• 批准号: BB/X007820/1
• 负责人: Faraz Mardakheh
• 金额: $ 80.81万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=BB%2FX007820%2F1
• 关键词: Deciphering; novel; interplay; between; RNA

Each cell in our body contains the same genetic information, yet this information is decoded in vastly different manners, allowing different cells to acquire distinct roles, which are together needed for the proper functioning of our tissues and organs. The genetic information is stored in DNA molecules, which reside in a part of the cell called the nucleus. In the nucleus, DNA is wrapped around a group of specialised proteins called histones, forming a DNA-protein structure known as chromatin. This protects the DNA from damage, and regulates access to the genetic information, which is crucial for determining which genes can be decoded at any given time. The packaging of chromatin therefore needs to be accurately controlled at all times, but it is not fully clear exactly his this is achieved in our cells.Our preliminary results have revealed that an important chromatin protein named histone H1 can also bind to RNA molecules. RNA molecules are intermediate molecules which mediate the decoding of genetic information from DNA, but recent findings suggest they can also control chromatin. Our aim now is to understand how histone H1 binds to RNA, and how this binding affects the decoding of genetic information and the structure of chromatin. To do this, we will use a variety of cutting-edge approaches to investigate how histone H1 interaction with RNA is regulated in cells. We will then reveal the impact of histone H1 binding to RNA on the decoding of genetic information. Finally, we will assess how changes in histone H1 function can control different cell behaviours such as cell-division. Addressing these fundamental questions will greatly advance our understanding of chromatin biology and its regulation, opening up new opportunities for modulating chromatin function in biotechnology (e.g. cell reprogramming) and medicine (new therapeutic targets).

我们身体中的每个细胞都包含相同的遗传信息，但这些信息以截然不同的方式解码，使不同的细胞获得不同的角色，这些角色是我们组织和器官正常运作所必需的。遗传信息存储在DNA分子中，DNA分子位于细胞的一部分，称为细胞核。在细胞核中，DNA包裹在一组称为组蛋白的特殊蛋白质周围，形成称为染色质的DNA-蛋白质结构。这可以保护DNA免受损害，并调节对遗传信息的访问，这对于确定在任何给定时间可以解码哪些基因至关重要。染色质的包装因此需要在任何时候都得到精确的控制，但目前还不完全清楚这在我们的细胞中是如何实现的。我们的初步结果显示，一种名为组蛋白H1的重要染色质蛋白也可以与RNA分子结合。RNA分子是介导从DNA解码遗传信息的中间分子，但最近的发现表明它们也可以控制染色质。我们现在的目标是了解组蛋白H1如何与RNA结合，以及这种结合如何影响遗传信息的解码和染色质的结构。为此，我们将使用各种尖端方法来研究组蛋白H1与RNA的相互作用如何在细胞中调节。然后，我们将揭示组蛋白H1与RNA结合对遗传信息解码的影响。最后，我们将评估组蛋白H1功能的变化如何控制不同的细胞行为，如细胞分裂。解决这些基本问题将大大推进我们对染色质生物学及其调控的理解，为生物技术（例如细胞重编程）和医学（新的治疗靶点）中调节染色质功能开辟新的机会。