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Mechanistic insights into tRNA thiolation catalyzed by iron-sulfur enzymes

石坂, 優人 北海道大学

2023.03.23

概要

1-1. Post-transcriptional modifications of RNA
In protein biosynthesis, various ribonucleic acids (RNA) are involved such as transfer
RNA (tRNA), messenger RNA (mRNA), and ribosomal RNA (rRNA). These RNAs do
not function immediately after transcription in vivo. Thus, immature RNA undergoes
enzymatic reactions called post-transcriptional processes including splicing and
modifications for maturation. Among these processes, more than 150 kinds of base/ribose
modifications have been discovered in RNA, and these modifications are the most diverse
in tRNA[1]. Recently, the relationship between abnormalities in tRNA modifications and
diseases has been reported[2,3]. Therefore, it is significant to understand the molecular
mechanisms of tRNA maturation.
1-2. tRNA modifications
During translation, tRNA transfers amino acids to ribosomes according to their
anticodon for protein biosynthesis. Immature tRNA undergoes post-transcriptional
processes such as splicing, CCA addition, ribose/base modification, and aminoacylation
(Fig. 1-1)[4]. For the ribose/base modification, more than 110 kinds of tRNA modifications
have been identified such as methylation, acetylation, and thiolation[1]. In particular,
diverse base modifications are found at position 1 of tRNA anticodon (position 3 of the
codon), and loss of these modifications reduces the translation rate, causing ribosomal
arrest and protein misfolding/aggregation[5]. ...

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Acknowledgements

I would like to appreciate my supervisor, Emeritus Professor Min Yao, who trained in

my bachelor's, master's, and doctoral programs even after her retirement. She respected

my initiative and provided me with various opportunities, allowing me to enjoy science

and acquire expertise in structural biology. She also taught me presentation skills for

various domestic and international conferences and scientific writing skills. I will work

harder in Germany from April 2023 and come back to Japan to repay your kindness.

I would also like to express my gratitude to my supervisor, Professor Toyoyuki Ose.

His useful advice on experimental techniques and discussions at lab meetings have greatly

advanced my research. He taught me not only the theory of crystallography, but also the

importance of applying the best approaches depending on research questions.

I wish to thank Professor Yoshikazu Tanaka (at Tohoku University) for a lot of support

including reviewing our papers. He also gave me an opportunity to enter the Ambitions

Leader’s Program (ALP), which widen my comprehensive perspective, including

QM/MM simulations and MD simulations. I am grateful to my collaborator, Associate

Professor Masaki Horitani (at Saga University) for EPR experiments. When I had trouble

with the results, he always responded sincerely to my questions.

For the establishment of the foundation of the TtuA project, I would like to express my

respect and gratitude to my predecessors, Dr. Minghao Chen and Mr. Shun Narai. I have

also learned countless things from them in terms of experimental techniques, analysis

methods, and even their research attitude. I would also like to thank Associate Professor

Koji Kato (at Okayama University) and Specially Appointed Associate Professor Jian Yu

(at Osaka University) for teaching me how to use various software for X-ray

crystallography. I also thank the beamline staff at the Photon Factory and SPring-8 for

their support. This work was supported by the Japan Society for the Promotion of Science

(JSPS), ALP, and the Nitobe School at Hokkaido University.

Thanks to the support of all members of my laboratory and friends, I was able to

continue my research and successfully complete my doctoral program. Finally, I would

like to thank my family, especially my parents, with all my heart for their continuous

dedication and support throughout the past 27 years.

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