Dr. Ma's team found that chemical modification of RNA (called RNA methylation) regulates mitochondrial function. Mitochondria is best known for generating energy in the cell. However, Dr. Ma explains, mitochondria does much more. It also acts as a signaling center that regulates broad biological processes within the cell. Dr. Ma's lab previously linked mitochondrial dysfunction to the development of SMA and autism, while other labs have implicated it in cancer pathogenesis.
"Our finding establishes a critical link between RNA methylation, mitochondria and diseases that relate to mitochondrial dysfunction, which means that now we have potential for new treatments for many different disorders," said Dr. Ma, who is the senior author on the study. He holds the Children's Research Fund Endowed Professorship in Neurobiology at Lurie Children's and is Associate Professor of Pediatrics, Neurology, and Neuroscience at Northwestern University Feinberg School of Medicine.
Dr. Ma's lab found that RNA methylation regulates mitochondrial function by controlling production of key enzymes that are components of mitochondria. They demonstrated in a neural stem cell model and a mouse model that loss of RNA methylation significantly changed mitochondrial function in stem cells and neurons.
"We are very excited about this discovery and the promise of innovative treatments, which could involve developing modifiers of RNA methylation to rectify the mitochondrial defect," said Dr. Ma. "We are also honored to contribute significantly to the study of RNA methylation. There is exponential growth in this field, and we hope that our ongoing research on RNA methylation in the nervous system will bring new insights on brain development and neurological disorders."
Research at Ann & Robert H. Lurie Children's Hospital of Chicago is conducted through Stanley Manne Children's Research Institute, which is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children's is a nonprofit organization committed to providing access to exceptional care for every child. It is ranked as one of the nation's top children's hospitals by U.S. News & World Report. Lurie Children's is the pediatric training ground for Northwestern University Feinberg School of Medicine.
Michael Kahl, Zhaofa Xu, Saravanan Arumugam, Brittany Edens, Mariafausta Fischietti, Allen C Zhu, Leonidas C Platanias, Chuan He, Xiaoxi Zhuang, Yongchao C Ma.
m6A RNA methylation regulates mitochondrial function.
Human Molecular Genetics, 2024. doi: 10.1093/hmg/ddae029