Biography
Biography: Zhongwei Li
Abstract
Statement of the Problem: Oxidation is probably the most common type of damage that occurs in cellular RNA. Oxidized RNA may be dysfunctional and is implicated in the pathogenesis of age-related human diseases. Cellular mechanisms controlling oxidized RNA have begun to be revealed. Currently, many ribonucleases and RNA-binding proteins have been shown to reduce oxidized RNA and to protect cells under oxidative stress. Although information about how these factors work is still very limited, we suggest mechanisms that can be used to minimize oxidized RNA in bacteria and human cells.
Methodology & Theoretical Orientation: RNA oxidation levels are determined by chromatographic separation of nucleosides and detection of 8-oxoG levels. Cell viability was determined by growth rate. Functions of ribonucleases and other proteins were studied by examining mutants lacking genes encoding these proteins, or over-expressing the genes.
Findings: Many ribonucleases and other proteins were found important for maintaining cell viability under oxidative stress. We have also identified proteins that specifically bind oxidized RNA at high affinity. In mutants lacking these activities, oxidized RNA accumulates. Over-expression of these activities reduces oxidized RNA and rescue cells under oxidative stress. Normalized RNA oxidation levels reduce overtime after pulse oxidative challenge.
Conclusion & Significance: The results demonstrate mechanisms for selective removal of oxidized RNA in bacteria and cultured human cells. Selective reduction of RNA oxidation depends on the activities of ribonucleases, suggesting that RNA degradation plays a major role in this process. The finding of specific proteins with high affinity to oxidized RNA implies that oxidized RNA is recognized by these proteins, targeting the RNA to effective degradation or repair. The findings demonstrate an important mechanism for maintaining RNA quality for normal function of the cell, and for prevention of related human diseases.