Oxidative stress is a major contributor to the production of constituents of the endogenous exposome. It is a result of an imbalance between the production and accumulation of reactive oxygen species (ROS) in cells and tissues. Oxidative stress is heavily regulated and various ROS which lead to damage to cellular components if uncontrolled. Reactive oxygen species have various sources both endogenous and exogenous. Endogenously, ROS can be produced in the endoplasmic reticulum, mitochondria, peroxisome and macrophages; whereas exogenously ROS can be generated in response to UV light, ionizing radiation, environmental pollutants, heavy metals and xenobiotics, such as antiblastic drugs. At the cellular level, the proliferation of ROS can cause damage to all macromolecules including lipids, proteins, DNA and RNA. To date, RNA oxidative damage has remained understudied, and yet an important area of research. Significant levels of RNA oxidative damage can be detected in aging animal models and patients with neurodegenerative diseases such as Alzheimer's and Parkinson′s disease. The aim of this research is to determine how the naturally occurring lesion O6-methylguanosine (m6G) in human U2 snRNA impacts its structure and function under conditions of oxidative stress. Specifically, an efficient synthetic method has been developed for a 5′-H-phosphonate-6-O-methyl-guanosine monomer, which can be incorporated into RNA oligonucleotides via novel reverse automated oligonucleotide synthesis. This substrate will facilitate the development of important tools for the further investigation of the impact of oxidative damage on RNA.

Design and synthesis of tools to assess the impact of 6-OMe guanosine on the stability of U2 snRNA under conditions of oxidative stress

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.