RNA Biology and Neuroscience
- Elucidation of the neurodegenerative diseases, especially amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia, along with development of therapies
- Development of RNA labeling technology to study selective neuronal death
- Understainding of biological significance of RNA methylation and RNA editing
- Application of noncoding RNAs such as miRNA as disease biomarkers
- Computational analysis to predict RNA secondary structures and target modification sites
The basic study for RNA biology by a combination of advanced molecular biology and bioinformatics analyses and its application for the elucidatation of the molecular mechanisms underlying neurodegenerative diseases.
Recent research has revealed that there might exist at least 1,500 RNA-binding proteins in the human body, which is far exceeding conventional predictions. Among these proteins, the targets and functions of more than half remain to be known. Interestingly, mutations in approximately 10% of the genes encoding RNA-binding proteins have been associated with human genetic diseases, and more than half of them affect the nerves and muscles. This evidence suggests that neurons and muscle cells are especially vulnerable to the dysregulation of RNA metabolism.
Representative diseases associated with the dysregulation of RNA metabolism include amyotrophic lateral sclerosis (ALS), frontotemporal lobe degeneration (FTLD), and spinocerebellar ataxia. In these neurodegenerative diseases, selective neurons are affected. Given that disease-associated RNA-binding proteins are usually ubiquitously expressed, the mechanims underlying selective neuronal death through the dysregulation of RNA metabolism remain unsolved. In addition, in the case of ALS and FTLD, an abnormal expansion of GGGGCC repeat sequence in the intron of C9orf72 gene has been identified. However, the disease mechanism mediated by this expansionn is largely undetermined (Figure 1). Our laboratory aims to elucidate the mechanisms through which the dysregulation of RNA metabolism cause selective neuronal death in some neurodegenerative diseases and to establish corresponding treatments. Part of this research depends on basic understanding of RNA regulation, which is why we also study basic RNA biology.
In addition to research on neurodegenerative diseases, our laboratory currently studies the functions and physiological importance of microRNAs and long noncoding RNAs, as well as ways to utilize these noncoding RNAs as disease biomarkers. We are also analyzing the biological significance of various modifications in RNA such as RNA editing and RNA methylation (Figure 2) by developing comprehensive analytical methods. Comprehensive analysis of RNA biology requires a combination of advenced molecular biology and bioinformatics. Therefore, we have established the room for the computational analysis and the appropriate staff was hired for the RNA bioinformatics. Overall, the laboratory is unique in its approach, which is acheived by deepening the study of basic RNA biology, to clarify the pathogeneis of and seek treatments for neurodegenerative diseases.