Creation of tools to determine the impact of natural modifications on RNA damage

创建工具来确定自然修饰对 RNA 损伤的影响

• 批准号: 1904754
• 负责人: Amanda Bryant-Friedrich
• 金额: $ 60万
• 依托单位: University of Toledo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904754&HistoricalAwards=false
• 关键词: Creation; tools; determine; impact; natural

The best-known role of RNA is to convert information stored in DNA to functional proteins. However, RNA has many other responsibilities in the cell. One group of RNAs with a less common role is small nuclear RNAs (snRNAs), which is found in the nucleus. The snRNA assists in cutting RNA into pieces, and these pieces then play roles in activating genes (for example). With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding a study by Dr. Amanda Bryant-Friedrich at the University of Toledo and Dr. Christine Chow at Wayne State University to study the protection of snRNAs from oxidative damage (damage from oxygen-containing species in the environment) that may harm cells. As a key part of this collaboration, Drs. Bryant-Friedrich and Chow train students, trainees and junior faculty from diverse backgrounds for their full participation in the scientific enterprise. While it is widely known that oxidative damage causes extensive modifications to DNA and impacts its structure and function, the same damage has not been actively explored in RNA. Due to the central nature of snRNAs in the assembly, structure, and function of the spliceosome, it is suspected that oxidative damage to snRNAs could cause lesions that impact both the structure and function of the spliceosome. Due to the high extent of post-translational modification of U2 sRNA, this small RNA is used as a prototype to determine the impact of the type and number of modifications on the outcomes of oxidative damage when compared to unmodified RNA. The effect of post-transcriptional modifications on the susceptibility of snRNA to oxidative damage is measured by a combination of synthetic, biophysical, biochemical, and analytical methods. This work may lead to new tools that can be used to understand oxidative damage in naturally-modified RNAs. The collaborative nature of the work and complementary scientific expertise of Bryant-Friedrich and Chow provide cross-mentoring opportunities for a range of trainees, particularly those from underrepresented groups who work at the chemistry-biology interface.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

RNA最著名的作用是将储存在DNA中的信息转化为功能蛋白质。然而，RNA在细胞中还有许多其他职责。一组作用不太常见的RNA是小核RNA（snRNA），它存在于细胞核中。snRNA协助将RNA切割成片段，然后这些片段在激活基因中发挥作用（例如）。有了这个奖项，化学部的生命过程化学项目正在资助托莱多大学的阿曼达·布莱恩特-弗里德里希博士和韦恩州立大学的克莉丝汀·周博士的一项研究，以研究snRNA免受可能伤害细胞的氧化损伤（环境中含氧物质的损伤）的保护。 Bryant-Friedrich博士和Chow博士培训来自不同背景的学生、学员和初级教师，让他们充分参与科学事业。虽然众所周知，氧化损伤导致DNA的广泛修饰并影响其结构和功能，但在RNA中尚未积极探索相同的损伤。由于snRNA在剪接体的组装、结构和功能中的中心性质，怀疑对snRNA的氧化损伤可能导致影响剪接体的结构和功能的病变。 由于U2 sRNA的翻译后修饰程度很高，这种小RNA被用作原型，以确定与未修饰的RNA相比，修饰的类型和数量对氧化损伤结果的影响。 转录后修饰对snRNA对氧化损伤的敏感性的影响通过合成、生物物理、生物化学和分析方法的组合来测量。这项工作可能会导致新的工具，可用于了解自然修饰的RNA中的氧化损伤。Bryant-Friedrich和Chow的合作性质和互补的科学专业知识为一系列学员提供了交叉指导的机会，特别是那些来自代表性不足的群体的化学生物学接口工作的学员。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。