When researchers look for the genetic causes of diseases impairing the ability of millions to speak, move, or think, investigators typically focus on the tiny part of the human genome linked to 25,000 or so protein-producing genes. Called the protein-coding region, this area accounts for less than 2 percent of the genome.
But, Jiaqian Wu, Ph.D., assistant professor at The University of Texas Health Science Center at Houston (UTHealth), believes there is much to be learned about demyelinating diseases like multiple sclerosis, spinal cord injury, and stroke in the other 98 percent of the genome.
Her team has been searching this poorly understood region for clues as to what causes nerve cells, or neurons, to misfire and has identified novel molecules tied to the development of the insulation of nerve cells. Findings appear in the journal PLOS Genetics.
“We believe this work is of great translational potential for regenerative medicine,” said Wu, who is on the faculty of the Vivian L. Smith Department of Neurosurgery and the Center for Stem Cell & Regenerative Medicine at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth.
The study focused on identifying novel long noncoding ribonucleic acid or LncRNAs and their roles in carrying out genetic instructions. Unlike traditional RNAs that make proteins (the body’s building blocks), LncRNAs are regulatory molecules that can control the transcription of hundreds of genes.
“Predicting LncRNAs’ function using cell type specific data revealed their potential functional roles in central nervous system development,” Wu said.
Researchers are particularly interested in how the body develops the tissue, or myelin, that protects long strands of nerve cells called axons. Much like the coating that guards electrical wires, exposed nerve cells can misfire.
Scientists are working on ways to replace that insulation, and Wu’s research could go a long way toward achieving that goal.
Some of the newly identified LncRNAs are important for neural stem cells to make oligodendrocyte precursor cells, which theoretically could be used to replace the missing myelin.
“This is the first LncRNA expression database of collective populations of glia, vascular cells, and neurons. We anticipate that these studies will advance the knowledge of this major class of non-coding genes and their role in neurological diseases,” she said.
Wu’s UTHealth co-authors include Xiaomin Dong, Ph.D.; Kenian Chen, Ph.D.; Raquel Cuevas-Diaz Duran, Ph.D.; Yanan You, Ph.D.; Shan Zong, Ph.D.; and Qilin Cao, M.D. The study is titled “Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination.”
Wu and Cao are on the faculty of the Mischer Neuroscience Institute at Memorial Hermann-Texas Medical Center. Wu is also on the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston.