Professor Fan-Yan WEI
Assistant Professor Akiko FUTAKUCHI

Our researches investigate the role of chemical modifications in RNA and their impact on human diseases. Various chemical modifications have recently been identified in RNA, which has been energizing a new research field known as “epitranscriptomics”. However, their physiological significance on humans remain unknown.

Currently, our researches focus on understanding the machinery involved in tRNA modification, as well as studying the mechanisms and consequences of dysregulation of tRNA modifications in aging-related diseases. Cytosolic and mitochondrial tRNAs contain sulfur-derived chemical modifications that are vital for protein translation. These modifications appear to be affected by redox status, and are altered during aging. Using a genome-wide screening system in combination with mouse models, we aim to identify the intracellular components responsible for sulfur insertion in tRNAs. In addition, we have discovered that tRNA modifications can be rapidly metabolized in response to stimuli, and dysregulation of tRNA modifications could potentially exaggerate novel cellular signaling, leading to altered protein translation. Using mass spectrometry in combination with physiological approaches, we are attempting to elucidate the underpinning mechanisms and biological consequences. We believe our work will broaden our knowledge of the biological principle of protein translation, and contribute to the development of therapeutic agents for aging-related diseases.

1. J. Clin. Invest. (2011) 121, 3598–3608.
2. Cell Metab. (2015) 21, 428–442.
3. Nucleic Acids Res. (2017) 45, 435–445.
4. Nat. Commun. (2017) 8, 1177.
5. Cell Rep. (2018) 22, 482–496.