Mechanism of transcription and related gene expression processes in bacteria and human mitochondria

细菌和人类线粒体的转录机制及相关基因表达过程

基本信息

项目摘要

Project Summary The synthesis of RNA by RNA polymerase (RNAP) and folding of that RNA into its biologically functional three- dimensional shape go hand in hand. The kinetics of RNA synthesis determine the folding outcome, and are influenced by myriad factors, such as intracellular temperature, pH, concentrations of small molecules and proteins in the cell, and the exact sequence of DNA being transcribed into RNA. Transcription is not a continuous process: RNA synthesis by RNAP is interrupted by sequence-dependent pauses, during which the polymerase remains bound to the nucleic acids without active nucleotide addition occurring. These pauses create windows of time for regulation of transcription to occur. Our research program will address at the atomic level the pausing mechanisms and contribution of pausing to co-transcriptional events, such as folding of RNA. The first direction of the program aims to develop tools for capturing and visualizing RNA folding intermediates during transcription and to understand the effect of pH on the kinetics of RNA synthesis by RNAP, and thus the RNA folding pathway. The resulting tools will be of broad interest to the RNA community because they can be applied to follow folding of other biologically important RNAs. The second direction will apply those tools to map co-transcriptional RNA folding differences in “healthy” and mutated human mitochondrial transfer RNAs (mt-tRNA), thus providing the structural basis for disease-causing mt-tRNA mutations. Additionally, we will assess the contribution of mitochondrial RNAP pausing to the differential folding of unmutated and disease-variant mt-tRNA, thus expanding the arsenal of regulatory roles transcriptional pausing plays in this key organelle. Finally, the third research direction will address how the balance between transcription of mitochondrial DNA and its packaging is achieved to cater to the ever-changing cellular needs for energy. The completion of the proposed research will be transformative to the understanding of the basic principles of gene expression, as well as to the applications in synthetic biology and to the molecular mechanisms of diseases linked to mitochondrial DNA.
项目摘要 通过RNA聚合酶(RNAP)合成RNA并将RNA折叠成具有生物学功能的三个- 三维形状齐头并进。RNA合成的动力学决定了折叠的结果, 受无数因素的影响,如细胞内温度,pH值,小分子的浓度, 细胞中的蛋白质,以及DNA被转录成RNA的确切序列。转录不是连续的 过程:RNAP的RNA合成被序列依赖性暂停中断,在此期间,聚合酶 保持与核酸结合而不发生活性核苷酸添加。这些停顿创造了窗口 转录调控的时间。我们的研究计划将在原子水平上解决 机制和暂停对共转录事件的贡献,如RNA的折叠。第一方向 该计划的目的是开发用于捕获和可视化转录过程中RNA折叠中间体的工具 并了解pH对RNAP合成RNA动力学的影响,从而了解RNA折叠途径。 由此产生的工具将引起RNA社区的广泛兴趣,因为它们可以用于跟踪折叠 其他重要的生物RNA。第二个方向将应用这些工具来绘制共转录RNA 在"健康的"和突变的人线粒体转移RNA(mt-tRNA)的折叠差异,从而提供了 致病mt-tRNA突变的结构基础。此外,我们还将评估 线粒体RNAP暂停未突变和疾病变异的mt-tRNA的差异折叠, 扩大了转录暂停在这个关键细胞器中发挥的调节作用。第三个 研究方向将解决如何线粒体DNA的转录和包装之间的平衡 是为了满足不断变化的细胞对能量的需求。完成拟议的研究 将对理解基因表达的基本原理以及 在合成生物学和与线粒体DNA相关的疾病的分子机制中的应用。

项目成果

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Tatiana Vladimirovna Mishanina其他文献

Tatiana Vladimirovna Mishanina的其他文献

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{{ truncateString('Tatiana Vladimirovna Mishanina', 18)}}的其他基金

Mechanism of transcription and related gene expression processes in bacteria and human mitochondria
细菌和人类线粒体的转录机制及相关基因表达过程
  • 批准号:
    10455073
  • 财政年份:
    2021
  • 资助金额:
    $ 0.76万
  • 项目类别:
Mechanism of transcription and related gene expression processes in bacteria and human mitochondria
细菌和人类线粒体的转录机制及相关基因表达过程
  • 批准号:
    10650405
  • 财政年份:
    2021
  • 资助金额:
    $ 0.76万
  • 项目类别:
Mechanism of transcription and related gene expression processes in bacteria and human mitochondria
细菌和人类线粒体的转录机制及相关基因表达过程
  • 批准号:
    10799077
  • 财政年份:
    2021
  • 资助金额:
    $ 0.76万
  • 项目类别:
Mechanism of transcription and related gene expression processes in bacteria and human mitochondria
细菌和人类线粒体的转录机制及相关基因表达过程
  • 批准号:
    10275389
  • 财政年份:
    2021
  • 资助金额:
    $ 0.76万
  • 项目类别:

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