Investigating the coordinated interplay of mRNA and tRNA modifications mediated by the FTO-TRMT10A complex

研究 FTO-TRMT10A 复合物介导的 mRNA 和 tRNA 修饰的协调相互作用

基本信息

  • 批准号:
    10252781
  • 负责人:
  • 金额:
    $ 4.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-01 至 2022-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract RNA modifications are concurrently found on nearly all RNA species and can dramatically alter the properties and expression of RNA. Modifications to mRNA can affect gene expression through several mechanisms such as localization, stability, and translation efficiency. Modifications to tRNAs are known to affect their stability and abundance as well as their decoding and elongation dynamics during translation. Dysregulation of many enzyme-mediated RNA modifications have been causally linked to impaired neurological development, intellectual disabilities, and behavioral abnormalities. There has been a great effort by the field to understand the functional impact of individual modifications in isolated RNAs, but the interplay of both mRNA and tRNA modifications has never been explored. The potential for cross-talk between modifications and RNA species echoes the combinatorial control seen in post-translational modifications. We have recently discovered that two distinct RNA-modifying enzymes, tRNA methyltransferase 10A (TRMT10A) and the mRNA demethylase Fat Mass and Obesity protein (FTO), interact and function together to control gene expression. These findings may represent a novel coregulatory mode of gene regulation accomplished by the coordinated RNA-modifying activity of TRMT10A and FTO. In order to better understand the functional role of this enzyme complex, we will (1) define the biochemical and structural parameters of this RNA-modifying complex and (2) elucidate which mechanism(s) underlie how gene expression is modulated by the activity of FTO-TRMT10A. The first goal will take advantage of the array of biophysical tools and expertise available to the Department of Biochemistry and Biophysics to obtain detailed molecular and structural characteristics of wild-type and mutant FTO-TRMT10A complexes. The second goal will be accomplished by employing a spectrum of molecular biology and biochemistry techniques in relevant cell lines to analyze RNA subcellular localization, stability, and modification profile changes. UPenn is an exceptional environment to support my training and this study, fostering a particularly collaborative campus of researchers that cross many intellectual and technical fields. The countless opportunities to learn techniques, use specialized equipment, form collaborations, and share ideas will continue to enrich my research and training. Overall, the tools, training, and expertise are all in place to successfully accomplish the goals set in this proposed study of the novel coregulation of mRNA and tRNA modifications.
项目摘要/摘要 几乎所有的RNA物种都可以同时发现RNA修饰,并能显著改变其性质 和RNA的表达。对mRNA的修饰可以通过几种机制影响基因表达,例如 作为本地化、稳定性和翻译效率。已知对tRNA的修饰会影响其稳定性和 丰度以及它们在翻译过程中的解码和伸长动态。许多人的调控失调 酶介导的RNA修饰与神经发育受损有因果关系, 智力残疾和行为异常。该领域已经付出了巨大的努力来理解 单个修饰对分离RNA的功能影响,但mRNA和tRNA两者的相互作用 修改从来没有被探索过。修饰和RNA物种之间可能存在的串扰 与翻译后修饰中看到的组合控制相呼应。我们最近发现有两个 不同的RNA修饰酶,tRNA甲基转移酶10A(TRMT10A)和mRNA去甲基酶脂肪 质量和肥胖蛋白(FTO)相互作用,共同发挥作用,控制基因的表达。这些发现可能 代表了一种通过协同RNA修饰实现的基因调控的新的协同调节模式 TRMT10A和FTO的活性。为了更好地了解这种酶复合体的功能作用,我们将 (1)确定该RNA修饰复合体的生化和结构参数;(2)阐明 基因表达受FTO-TRMT10A活性调控的机制(S)。第一个目标将是 利用一系列生物物理工具和专业知识供生物化学系和 获得野生型和突变型FTO-TRMT10A详细分子和结构特征的生物物理研究 复合体。第二个目标将通过使用一系列分子生物学和 相关细胞系中分析RNA亚细胞定位、稳定性和修饰的生化技术 配置文件更改。宾夕法尼亚大学是一个特殊的环境来支持我的培训和这项研究,培养 特别是跨越许多智力和技术领域的研究人员的协作校园。无数的人 学习技术、使用专门设备、形成协作和分享想法的机会将 继续丰富我的研究和培训。总体而言,工具、培训和专业知识都已到位,以 成功地完成了这项新的mrna和trna共同调节研究中设定的目标 修改。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
TET-mediated 5-methylcytosine oxidation in tRNA promotes translation.
  • DOI:
    10.1074/jbc.ra120.014226
  • 发表时间:
    2021-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Shen H;Ontiveros RJ;Owens MC;Liu MY;Ghanty U;Kohli RM;Liu KF
  • 通讯作者:
    Liu KF
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Robert Jordan Ontiveros其他文献

Robert Jordan Ontiveros的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 4.17万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了