Impact of chemical modification of non-coding RNAs on gene expression in S. pombe

非编码 RNA 化学修饰对粟酒裂殖酵母基因表达的影响

• 批准号: RGPIN-2020-06064
• 负责人: Bayfield, Mark
• 金额: $ 2.33万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718227
• 关键词: Impact; chemical; modification; non; coding

Cells have evolved a number of diverse mechanisms by which they ensure the stable expression of genes that are critical to life, as well as complex schemes by which they can vary such processes in order to adapt to environmental conditions and stresses. Many of these mechanisms and processes are highly conserved throughout evolution. It is often then much simpler and more straight-forward to study these critical processes using single-celled eukaryotes from which we can then extrapolate insights into how related processes are controlled in higher eukaryotes, like humans. In our proposed work, we plan to use the simple yeast Schizosaccharomyces pombe to investigate how specific chemical reactions contribute to the stable maintenance of components of the intracellular machinery that are used to control gene expression. More specifically, we propose to study a number of conserved but poorly characterized enzymes that are responsible for the chemical modification of RNA molecules that comprise critical components of the gene expression infrastructure. One class of enzymes we will study is responsible for the chemical modification of transfer RNAs (tRNAs), which are molecules that play critical roles in the synthesis of proteins in all life forms examined. These enzymes are hypothesized to promote tRNA stability and play a role in tRNA quality control, and so our proposed work will lead to new insights into how cells ensure that the machinery used to synthesize proteins is correctly generated. We also plan to investigate another class of methyltransferases that modify other types of non-coding RNAs but whose precise function and importance are not well understood. The evolutionary conservation of these enzymes is unusual: they are present in some organisms but not others, even though the known targets of the enzyme are universal and critically important to cellular growth. By studying the evolutionary conservation of these RNA modification enzymes and their targets in Schizosaccharomyces pombe, we will arrive at a better understanding of how life has evolved to promote robust synthesis of the machinery used to express genes as well as the quality control mechanisms in place to ensure this is done correctly. The elucidation of these mechanisms in yeast will be useful in extrapolating related pathways in higher organisms, and may assist in the generation of new tools for genetic engineering, as well in the design of new anti-microbials.

细胞已经发展出许多不同的机制，通过这些机制，它们可以确保对生命至关重要的基因的稳定表达，以及它们可以改变此类过程以适应环境条件和压力的复杂方案。 在整个进化过程中，许多这些机制和过程都高度保守。 然后，使用单细胞真核生物研究这些关键过程通常会更简单，更直接，然后我们可以从中推断出对相关过程如何在像人类（人类）等较高的真核生物中控制相关过程的见解。 在我们提出的工作中，我们计划使用简单的酵母菌型糖果POMBE来研究特定的化学反应如何促进用于控制基因表达的细胞内机械组件的稳定维护。 更具体地说，我们建议研究许多保守但特征性较差的酶，这些酶负责构成基因表达基础设施的关键成分的RNA分子的化学修饰。 我们将研究的一类酶负责转移RNA（TRNA）的化学修饰，这些酶在所检查的所有生命形式中都在蛋白质合成中起关键作用。 假设这些酶可以促进tRNA稳定性并在tRNA质量控制中发挥作用，因此我们提出的工作将导致对细胞的新见解，以确保如何正确生成用于合成蛋白质的机械。 我们还计划研究另一类甲基转移酶，以修改其他类型的非编码RNA，但其精确的功能和重要性尚不清楚。 这些酶的进化保护是不寻常的：尽管酶的已知靶标对于细胞生长是普遍的，但它们存在于某些生物中，而不是其他生物中。 通过研究这些RNA修饰酶的进化保护及其在schizosacchachomyces pombe中的靶标，我们将更好地了解生命如何进化以促进用于表达基因的机械以及质量控制机制的强大合成，以实现质量控制机制确保正确完成。在酵母中阐明这些机制将有助于推断高等生物的相关途径，并可能有助于生成新的基因工程工具，以及新的抗微生物的设计。