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最著名的作用是将存储在DNA中的信息转换为功能蛋白。但是，RNA在细胞中还有许多其他责任。一组具有较不常见作用的RNA是小核RNA（SNRNA），它在核中发现。 SNRNA有助于将RNA切成碎片，然后这些碎片在激活基因中起着作用（例如）。通过该奖项，化学司的化学过程计划为托莱多大学的阿曼达·布莱恩特·弗里德里奇（Amanda Bryant Friedrich）博士和韦恩州立大学的克里斯汀·乔（Christine Chow）提供了一项研究，以研究SNRNA免受氧化损害（对环境中含氧物种的损害）的保护，可能会损害细胞的细胞。 作为这项合作的关键部分，博士。布莱恩特·弗里德里奇（Bryant-Friedich）和乔（Chow）培训来自不同背景的学生，学员和初级教师，以全面参与科学企业。尽管众所周知，氧化损伤会引起广泛的DNA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害。由于SNRNA在剪接体的组装，结构和功能中的核心性质，因此怀疑对SNRNA的氧化损害可能会导致损伤，从而影响剪接体的结构和功能。 由于U2 SRNA的翻译后修饰程度很高，与未修改的RNA相比，该小RNA用作确定修饰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是通过合成，生物物理，生化和分析方法的组合来衡量的。这项工作可能会导致新工具，可用于了解自然修饰的RNA中的氧化损伤。 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.