m6A mRNA modifications and myogenesis

m6A mRNA 修饰和肌生成

基本信息

  • 批准号:
    10013127
  • 负责人:
  • 金额:
    $ 16.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-09 至 2022-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA and long noncoding RNAs. m6A is induced by the Mettl3 complex most commonly near stop codons and 3’ UTRs in mRNAs. m6A recruits the YTH domain family of m6A-binding proteins, which then control almost every aspect of RNA metabolism, including alternative splicing, nuclear export, stability, and translation. Several thousand mRNA regions are modified by m6A in a given cell population, primarily at the consensus sequence of DRACH (D=A, G, or U; R=A or G; H=A, C, or U). Reflecting the diverse molecular functions of m6A, it also regulates a wide range of biological phenomena, such as cancer cell proliferation, neural development, and pluripotent stem cell differentiation. However, the roles of m6A in muscle cell differentiation remain largely elusive. The PI’s group recently found that one of the Fkbp family member of peptidyl prolyl isomerases interacts with the Mettl3 complex. In addition, depletion of the Fkbp inhibited myoblast differentiation and decreased the total level of m6A in the cells, both of which were recapitulated by Mettl3 depletion. At a molecular level, the Fkbp promotes cis-trans isomerization of Mettl3 and its related protein Mettl14 in vitro. Based on these findings, they hypothesized that the Fkbp regulates the m6A level of myoblast mRNAs through isomerization of Mettl3 and Mettl14. Three aims were proposed to investigate this hypothesis. Aim 1 will determine genome-wide distribution of m6A in myoblasts at a single nucleotide level and study how the pattern changes by depletion of the Fkbp. Aim 2 will characterize how m6A affects metabolism of several most abundantly modified myoblast-specific mRNAs. Aim 3 will study how Fkbp8 regulates Mettl3 and Mettl14, focusing on phosphorylation and isomerization of the proteins. These studies are expected to lay a solid foundation for a future study of the roles of m6A in muscle cells.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Nobuaki Kikyo其他文献

Nobuaki Kikyo的其他文献

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{{ truncateString('Nobuaki Kikyo', 18)}}的其他基金

RNA methylation and mesenchymal stem cell differentiation
RNA甲基化与间充质干细胞分化
  • 批准号:
    10549380
  • 财政年份:
    2020
  • 资助金额:
    $ 16.94万
  • 项目类别:
RNA methylation and mesenchymal stem cell differentiation
RNA甲基化与间充质干细胞分化
  • 批准号:
    10331032
  • 财政年份:
    2020
  • 资助金额:
    $ 16.94万
  • 项目类别:
Regulation of hypoxic response by HIF isomerization
HIF 异构化调节缺氧反应
  • 批准号:
    9813473
  • 财政年份:
    2019
  • 资助金额:
    $ 16.94万
  • 项目类别:
Transcriptional elongation and long noncoding RNA
转录延伸和长非编码RNA
  • 批准号:
    9226044
  • 财政年份:
    2016
  • 资助金额:
    $ 16.94万
  • 项目类别:
Transcriptional elongation and long noncoding RNA
转录延伸和长非编码RNA
  • 批准号:
    9111196
  • 财政年份:
    2016
  • 资助金额:
    $ 16.94万
  • 项目类别:
Hypoxia and long noncoding RNA
缺氧和长非编码RNA
  • 批准号:
    8752852
  • 财政年份:
    2014
  • 资助金额:
    $ 16.94万
  • 项目类别:
Hypoxia and long noncoding RNA
缺氧和长非编码RNA
  • 批准号:
    8883446
  • 财政年份:
    2014
  • 资助金额:
    $ 16.94万
  • 项目类别:
Histone isomerization and pluripotency
组蛋白异构化和多能性
  • 批准号:
    8291578
  • 财政年份:
    2012
  • 资助金额:
    $ 16.94万
  • 项目类别:
Histone isomerization and pluripotency
组蛋白异构化和多能性
  • 批准号:
    8678949
  • 财政年份:
    2012
  • 资助金额:
    $ 16.94万
  • 项目类别:
Histone proline isomerization and gene regulation
组蛋白脯氨酸异构化和基因调控
  • 批准号:
    7566297
  • 财政年份:
    2009
  • 资助金额:
    $ 16.94万
  • 项目类别:

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