INTERNATIONAL JOURNAL OF ONCOLOGY 00: 000, 0000

Cover legend: Yasuhiro Furuichi; a member of The Editorial Academy ofThe International Journal of Oncology

Dr Yasuhiro Furuichi made an important fundamental discoveryof mRNA m7G-cap structure (Furuichi Y, Proc Jpn Acad Ser B
91: 394-408, 2015). In 1973, at the National Institute ofGenetics in Japan, he first observed that mRNA synthesis of
insect virus (CPV) that infects silkworm was stimulated in vitro
by methyl donor S-adenosylmethionine and the resulting
mRNAs were methylated at the 5'-termini. Based on theseunique findings, Dr Furuichi proposed the hypothesis‘Methylation-coupled transcription theory’ (Furuichi Y, Nucleic
Acids Res 1: 809-822, 1974), which was later proven true, as theeukaryotic transcriptome was found to consist of RNApolymerase and methyl transferase, and the resulting mRNAs
were methylated. In 1975, he identified the 5'-structure ofm7GpppAm in CPV mRNA (Furuichi Y and Miura K, Nature
253: 374-375, 1975), and m7GpppGm in human reovirus mRNA(Furuichi Y, et al, Proc Natl Acad Sci USA 72: 362-366, 1975),
and after he joined Dr Aaron J. Shatkin's laboratory at Roche
Institute of Molecular Biology in USA, he discovered the samestructures in eukaryotic cell and viral mRNAs, as well as theirprecursor RNAs in the nucleus (Furuichi Y, et al, Proc Natl
Acad Sci USA 72: 1904-1908, 1975). He gave such a blockedand methylated structure the nickname CAP. After he confirmed
the ubiquitous existence of cap in eukaryotic mRNAs, heelucidated the enzymatic pathway of cap synthesis in reovirustranscription which turned out identical to the cellular mRNAcap synthesis (Furuichi Y, et al, J Biol Chem 251: 5043-5053,1976). Furthermore, in 1977, he and his colleagues demonstrated
that the role of cap is essential for stabilizing mRNAs byprotecting them from degradation by a 5'‑3' exonuclease and forfacilitating mRNA translation by binding to the initiation factor

eIF4E in the protein synthesis (Furuichi Y, et al, Nature 266:235-239, 1977). These essential frameworks established by
Dr Furuichi in the 1970s have supported the understanding of
the mRNA capping and translation. The basic contributions
made by Dr Furuichi also stimulated drug discoveries, such as
the recent anti-influenza virus drug, Xofluza, a cap-dependentendonuclease inhibitor, by a pharmaceutical company which
has thus far saved as many as 5 million of virus-infectedindividuals in the winter season of 2019. For the virus researchcommunity, he served as the associated editor in the Journal ofVirology during the term 1980-1985.
After these epoch-making studies in mRNA capping
research in the USA, he returned to Japan in 1984 and worked in
the Roche drug discovery program. He collaborated withDr Martin Clozel at Roche in Basel, and formed a Swiss/Japan
joint team and found the miracle drug, Bosentan (an endotheline
antagonist), which had eased the suffering and pain of many
patients with pulmonary hypertension (Breu V, et al, Eur J
Biochem 231: 266-270, 1995). In 1993, being asked by a sectorof the Japanese government, Dr Furuichi began a research
consortium at AGENE research institute and challenged aninnovative positional cloning to identify the genes whosemutations cause premature aging syndromes. During his sevenyears at AGENE, Dr Furuichi and his team elucidated that theRecQ DNA helicase family consists of five independent
helicases, RecQ1, WRN, BLM, RTS and RecQ5, and they are
involved in various DNA repair processes to play an importantrole in stabilization of human genome in a tissue-dependent andin an enzyme function-dependent manner. These works were
published in approximately 100 publications and greatly
contributed to the understanding of the importance of DNA
repair in human aging and the development of cancers(Shimamoto A, et al, Int J Clin Oncol 9: 288-298, 2004).
Thus, Dr Furuichi is an excellent discovery hunter in thebasic research field of biology, in which he also contributed tothe applied science for the discovery of innovative medicines,
such as Bosentan and Xofluza. Currently, in spite of his greatage, he has been challenging the development of innovative
anti-cancer siRNA drugs (Futami K and Furuichi Y, Front
Genetics, doi:10.3389/fgene, 2015). Apart from these known
research activities, he has been serving as an excellent mentor toencourage many young scientists worldwide in the public
Research Programs.