Research

Higher-order biological processes, including development, differentiation and complex mental activity, are the result of sophisticated regulation of gene expression. Dysregulation of gene expression often causes a variety of human diseases. RNA molecules are deeply involved in regulation of gene expression at various steps of central dogma. We are tackling to elucidate various biological phenomena associated with RNA functions based on multidisciplinary approaches including molecular biology, biochemistry, genetics, analytical chemistry and cell biology.

RNA modifications associated with various biological functions :

RNA molecules are frequently modified post-transcriptionally, and these modifications are required for proper RNA functions. To date, over 140 different types of chemical modifications have been identified in various RNA molecules across all domains of life. We are studying biological processes associated with RNA modifications through discovery of novel RNA modifications and RNA-modifying enzymes using our original techniques for RNA isolation and analyses. So far, we reported seven novel RNA modifications, and over 40 RNA-modifying enzymes, and continue studying biogenesis and physiological roles of these modifications.

Decoding of genetic information and protein synthesis :

Genetic information in DNA is transcribed to mRNA, and then translated to protein on the ribosome. In general, fidelity of translation is estimated in the range of 10^-4 to 10^-5 per codon. Living organisms have various measures to maintain accuracy of protein synthesis. We are exploring novel tRNA modifications required for accurate decoding, and studying molecular function and physiological significance of these modifications. In addition, we are studying a novel quality control mechanism to maintain accurate translation in the cell using genetics and biochemistry.

Molecular pathogenesis of RNA modopathy :

It is a critical basic research to understand pathogenesis of human disease at molecular level for the purpose of development of effective therapeutic measures and diagnostic techniques. We previously revealed that lack of RNA modification is a primary cause of human diseases. This is the first confirmation of a human diseases caused by an RNA modification disorder. Thus, we are proposing "RNA modopathy" as a new category of human diseases. We are striving to reveal molecular pathogenesis of various RNA modopathies through multidimensional approaches using clinical specimens, patient tissues and cells, and knockout mice.

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