A Platform for Identifying GlycoRNA and Identifying Biases in RNA Pulldown Experiments

用于识别 GlycoRNA 和识别 RNA Pulldown 实验中偏差的平台

基本信息

  • 批准号:
    BB/X012883/1
  • 负责人:
  • 金额:
    $ 129.51万
  • 依托单位:
  • 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

项目摘要

Two of the biopolymers that are essential for the existence of life RNA and carbohydrates. RNA, a key player in the "central dogma" of biology, is transcribed from DNA and translated into proteins. However, RNA plays many more roles in biology, for instance as a messenger molecule or as a catalyst for cellular processes. Carbohydrates (sometimes known as "glycans") are traditionally thought of as a source of energy - although they also play many other important roles in regulation and protein folding. Until recently, these two crucial biopolymers were not thought to have shared an interface. New work has challenged this view, pointing toward RNA polymers that are functionalised with glycans. The implications of this new hybrid biopolymer (termed "glycoRNA") are currently unknown, but it could potentially play roles in understanding the fundamental biology of diseased states or in the development of technologies such as vaccines. Here, we propose a new method for studying glycoRNA, by using a strategy of targeting RNA with small molecules. The approach holds numerous advantages - it allows targeting a much larger fraction of the genome than protein-based approaches and holds the promise for being much more selective than DNA-based approaches.We recently discovered that a commonly-used technique in the field of studying RNA modifications, and indeed in many studies in the general area of chemical biology, may present some previously unknown biases. A molecule called DBCO is often used to enrich target RNA of interest, but we have found that DBCO may preferentially bind to some large RNA transcripts. We are worried this may be affecting the results of researchers around the world and we intend to carefully quantify this interaction and find ways to avoid the bias of future studies. We also intend to find out which different types of sugars can be found in glycoRNA. Sugars take on a diverse array of structures, from the well-known glucose to other, but related, ones such as galactose and mannose. We believe one of these sugars may be present in particularly high levels in glycoRNA and we plan to determine whether this is the case.Finally, once we have developed a robust method for identifying the different forms of glycoRNA, we plan to study how prevalent they are in different kinds of environments. These environments could be things such as different cell-types, or even in healthy versus unhealthy cells. If glycoRNA levels are found, for instance, to be present at different levels in unhealthy cells, they could potentially be used a diagnostic tool to identify disease. This approach will facilitate both basic and translational research at the intersection of chemistry, biology and pathology.
生命核糖核酸和碳水化合物赖以生存的两种生物聚合物。RNA是生物学“中心信条”中的一个关键角色,它由DNA转录而成,然后翻译成蛋白质。然而,RNA在生物学中扮演着更多的角色,例如作为信使分子或作为细胞过程的催化剂。碳水化合物(有时也被称为“多糖”)传统上被认为是一种能量来源--尽管它们在调节和蛋白质折叠方面也扮演着许多其他重要的角色。直到最近,这两种至关重要的生物聚合物还被认为没有共同的界面。新的工作挑战了这一观点,指出RNA聚合物是用多聚糖功能化的。这种新的杂交生物聚合物(称为“糖RNA”)的含义目前尚不清楚,但它可能在理解疾病状态的基础生物学或疫苗等技术的发展中发挥作用。在这里,我们提出了一种研究糖RNA的新方法,即利用小分子靶向RNA的策略。该方法具有许多优点--它允许靶向基因组中比基于蛋白质的方法要大得多的部分,并有望比基于DNA的方法更具选择性。我们最近发现,在研究RNA修饰领域的一种常用技术,甚至在化学生物学一般领域的许多研究中,可能会出现一些以前未知的偏差。一种名为DBCO的分子经常被用来丰富感兴趣的目标RNA,但我们发现DBCO可能优先与一些大的RNA转录本结合。我们担心这可能会影响世界各地研究人员的结果,我们打算仔细量化这种相互作用,并找到避免未来研究偏见的方法。我们还打算找出在糖核糖核酸中可以发现哪些不同类型的糖。糖具有各种各样的结构,从众所周知的葡萄糖到其他相关的结构,如半乳糖和甘露糖。我们认为这些糖中的一种可能存在于糖RNA中特别高的水平,我们计划确定是否如此。最后,一旦我们开发出一种强大的方法来识别不同形式的糖RNA,我们计划研究它们在不同环境中的普遍程度。这些环境可能是不同类型的细胞,甚至是健康和不健康的细胞。例如,如果在不健康的细胞中发现不同水平的糖RNA,它们可能被用来作为一种诊断工具来识别疾病。这种方法将促进化学、生物学和病理学交叉领域的基础研究和翻译研究。

项目成果

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Gonçalo Bernardes其他文献

Acute Myeloid and Lymphoblastic Leukemias: A NPM1 Targeting Strategy
  • DOI:
    10.1182/blood-2023-172497
  • 发表时间:
    2023-11-02
  • 期刊:
  • 影响因子:
  • 作者:
    Marta Leal Bento;Luís Carvalho;Zhewei Chen;Ana Coelho;Cong Tang;Gonçalo Bernardes
  • 通讯作者:
    Gonçalo Bernardes

Gonçalo Bernardes的其他文献

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{{ truncateString('Gonçalo Bernardes', 18)}}的其他基金

A Conditionally Activable Small Molecule Pro-Drug Conjugate for Targeted Treatment of Pancreatic Cancer
用于胰腺癌靶向治疗的条件激活小分子前药偶联物
  • 批准号:
    EP/Y036336/1
  • 财政年份:
    2024
  • 资助金额:
    $ 129.51万
  • 项目类别:
    Research Grant
A chemistry-driven approach to Senolytic Bispecific T-Cell Engagers
化学驱动的 Senolytic 双特异性 T 细胞接合剂方法
  • 批准号:
    EP/Y024699/1
  • 财政年份:
    2023
  • 资助金额:
    $ 129.51万
  • 项目类别:
    Fellowship
EPSRC-Royal Society Fellowship Engagement (2013): Site-specific fluorination of peptides and proteins
EPSRC-皇家学会奖学金参与 (2013):肽和蛋白质的位点特异性氟化
  • 批准号:
    EP/M003647/1
  • 财政年份:
    2014
  • 资助金额:
    $ 129.51万
  • 项目类别:
    Fellowship

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