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

RNA最著名的作用是将储存在DNA中的信息转化为功能性蛋白质。然而，RNA在细胞中还有许多其他职责。一组不太常见的rna是小核rna (snrna)，它存在于细胞核中。snRNA协助将RNA切割成碎片，然后这些碎片在激活基因（例如）中发挥作用。有了这个奖项，化学部门的生命过程化学项目资助了托莱多大学的Amanda Bryant-Friedrich博士和Wayne州立大学的Christine Chow博士的一项研究，研究snrna免受氧化损伤（环境中含氧物种的损伤）的保护，这可能会损害细胞。作为此次合作的关键部分，dr。布莱恩特-弗里德里希和周培训来自不同背景的学生、学员和初级教员，使他们充分参与科学事业。虽然众所周知，氧化损伤会导致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、结构和功能中的核心性质，我们怀疑snrna的氧化损伤可能导致影响剪接体结构和功能的病变。由于U2 sRNA的翻译后修饰程度很高，因此与未修饰的RNA相比，该小RNA被用作确定修饰类型和数量对氧化损伤结果的影响的原型。转录后修饰对snRNA氧化损伤易感性的影响是通过合成、生物物理、生化和分析方法的结合来测量的。这项工作可能会导致新的工具，可用于了解氧化损伤的自然修饰rna。工作的协作性质和Bryant-Friedrich和Chow的互补科学专业知识为一系列受训者提供了交叉指导的机会，特别是那些在化学-生物学界面工作的代表性不足的群体。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.