KAIST “Controlling degenerative diseases through mitochondria”

A domestic research team has discovered a new regulatory mechanism of mitochondrial double-stranded RNA in Korea. It is expected to help establish strategies for immune system modulation, management of degenerative diseases, and treatment. According to Professor Kim Yoo-sik’s team at KAIST’s Department of Life Chemical Engineering on the 22nd, mitochondrial double-stranded RNA is known to induce abnormal immune activity, leading to inflammation and cell death. When mitochondrial double-stranded RNA escapes into the cytoplasm under stress conditions, it triggers abnormal immune activity and cell death. In academia, immune activity triggered by mitochondrial double-stranded RNA has been reported to play a key role in the onset and progression of inflammatory degenerative diseases and autoimmune diseases such as rheumatoid arthritis, Huntington’s disease, and Sjogren’s syndrome. However, the molecular regulatory mechanism of mitochondrial double-stranded RNA has not been reported yet. The research team investigated the expression of each protein that exists inside mitochondria and can bind with RNA by inhibiting the expression of each protein using gene scissors, and found that the expression of mitochondrial double-stranded RNA significantly increased when the expression of a protein called NSUN4 was decreased. NSUN4 is known as one of the components of RNA that induces the chemical modification of cytosine. In particular, the research team first revealed that NSUN4 rapidly modifies mitochondrial non-encapsulated RNA that does not produce proteins. Additionally, through further research, the team confirmed that the decrease in the expression of mitochondrial RNA proteins increases the amount of mitochondrial double-stranded RNA, and leaked mitochondrial double-stranded RNA in the cytoplasm activates the immune response. The research team explained that they were able to propose a regulatory mechanism of expression through modification of mitochondrial double-stranded RNA, which has recently begun to attract attention as a new intracellular immune factor. Professor Kim Yoo-sik said, “The achievement of this study is revealing the formation and regulation mechanism of mitochondrial double-stranded RNA,” and expressed hope that effective strategies for controlling the onset and progression of immune system diseases and various degenerative diseases could be proposed based on the research results. This study was conducted with support from the National Research Foundation of Korea’s Excellent Young Researcher Support Program and the National Institutes of Health in the United States.