Masayasu Nomura. Photo courtesy of Daniel A. Anderson/UCI.
Masayasu Nomura was born in Japan in April of 1927 and died on Nov.19 in California, where he was a professor of biochemistry at the University of California-Irvine. He was a pioneer in ribosome research, a brilliant experimentalist, and a mentor to two generations of graduate students and postdocs who have been outstanding contributors to the life sciences.
Nomura received his bachelor’s and doctoral degrees from the University of Tokyo in the years when Japan was still emerging from the privations of World War II, and he thought he was destined to spend his life in hardscrabble labs working on projects related to agriculture or pharmacology, but his curiosity, scholarliness and bench smarts led to the opportunity to visit the United States in 1957 as a 30-year-old postdoctoral student. During a three-year sojourn in the U.S., Nomura worked with three towering figures in the burgeoning field of molecular biology: Sol Spiegelman, Jim Watson and Seymour Benzer. He discovered that he could hold his own at the frontiers of molecular biology research (1).
I was a graduate student at Caltech when I first saw Masayasu. He gave a seminar to Max Delbrück’s group on the work he had done with Benzer. He showed that rII deletions of bacteriophage T4 behaved as one would expect real physical deletions to behave – in crosses, the presence of a deletion in both parents shortened the recombination distance between flanking genetic markers. It was the sort of muscular, purely genetic experimental work that we admired in the Delbrück lab. Masayasu definitely passed the Delbrück test, according to which most seminars were met with “worst seminar I ever heard.” Nomura, on the other hand, he declared excellent.
In the early 1960s, the genetics department at the University of Wisconsin-Madison was searching for a replacement for Ernst Freese, who had moved to the National Institutes of Health. The department somehow got permission to hire two people to fill the vacancy. I was one of them, and Masayasu was the other. I was delighted to learn that he was going to be my colleague in Madison, but I had no idea how much Masayasu would enrich my life. He was my neighbor on the third floor of the genetics building from 1963 until 1971 (when he moved a few blocks west to the Institute for Enzyme Research), and for eight years I had a front-row seat at one of the greatest science shows on Earth.
Although Masayasu had done some work on ribosomes before coming to Madison, his early work in Madison focused on colicins – bacteriocidal products produced by bacteria. Nomura feared that the ribosome field would be a rat race and believed that work on colicins would be the secret to a tranquil life in science. The work he did on colicins was fascinating. He studied three different colicins and discovered that they killed target bacteria by three different mechanisms (1). This promised to be a rich field of investigation, and I think it’s fair to say that colicins were at least warm, if not rat-race hot, in the early 1960s, thanks to the work of the Nomura lab.
But Masayasu couldn’t resist the enticements of the ribosome. In parallel with his colicin work, he did a few wind-up experiments on ribosomes and, in the process, got hooked. The Nomura lab quickly became one of the leading centers for ribosome research, producing one dazzling discovery after another. In his pre-Madison work, Nomura had found that some ribosomal proteins could be reversibly stripped from the 30S and 50S ribosome subunits, leaving smaller, core subunits of sizes 23S and 40S. In Madison, he showed that when these stripped proteins were added back to the core subunits, they yielded fully active 30S and 50S subunits (2). Nomura then demonstrated that the 70S ribosome that was formed by association of the 30S and 50S subunits could not directly enter into protein synthesis; the initiation of protein synthesis was a stepwise process in which the messenger RNA first formed a complex with a 30S subunit and an initiator transfer-RNA; only after that complex formed could the 50S subunit enter into the complex (3).
Nomura and his colleagues managed completely to disassemble and then reassemble the 30S ribosomal subunit of E. coli, demonstrating that the 22 parts of the subunit (a 16S RNA molecule and 21 different proteins) contained all the information needed to assemble all the parts into a functional whole (4). Later, the Nomura lab achieved the total reconstitution of functional 50S ribosomal subunits of B. stearothermophilus from a mixture of separated components (two RNA molecules and about 30 different proteins) (5). These were landmark experiments on the self-assembly of complex biological structures. Toward the end of his years in Madison, Nomura examined the mechanism by which E. coli matches the rate of synthesis of ribosomal proteins with the rate of synthesis of ribosomal RNA. Much to everyone’s surprise, it turned out that the regulation was at the level of translation: Several of the ribosomal proteins, if present in excess of the number needed to form ribosomes, would bind specifically to the messenger RNAs encoding ribosomal proteins and repress translation of ribosomal protein message (6).
I had the privilege of reading many of Masayasu’s draft manuscripts describing these brilliant experiments. They came to me typed on yellow paper of the sort that was once used for carbon copies. The manuscripts were collages, assembled from small scraps that were taped together. Masayasu would first write and then rearrange his text by cutting and taping. The manuscripts had a wonderful, subtle aroma that I took to be some sort of soap or aftershave that Masayasu used, but I finally discovered that it was the odor of Scotch Magic Mending Tape, which I had never encountered in large quantity until I read his cut-and-tape manuscripts. Whatever the mechanism of their assembly, these draft manuscripts – not unlike ribosomes – ended up so well constructed that you could hardly imagine any way to improve them. Reading Masayasu’s manuscripts was a lesson in recognizing important problems, and the wonderful logic of his writing could evoke in the reader’s mind the transitory delusion that the reader could think (almost) as clearly as Masayasu.
Madison lost something irreplaceable when Nomura moved away. I pointed out at his goodbye party that “Nomura” is an anagram for “Our Man” and promised that we would always think of him as our man in Irvine. At Irvine, Nomura continued to work on ribosomes, but he turned from bacteria to yeast. He continued to be a major force in ribosome research and was active in research until the very end, discovering that the molecular genetics of yeast ribosomes was significantly different from that of bacteria and rejoicing at all the surprises that he encountered.
Nomura was much honored. He was elected to the National Academy of Sciences, the American Academy of Arts and Sciences, the American Academy of Microbiology, the Royal Netherlands Academy of Arts and Sciences, and the Danish Academy of Arts and Sciences. In 2002, he received the Abbott-ASM Lifetime Achievement Award from the American Society for Microbiology.
Masayasu is survived by his wife, Junko, his daughter, Keiko, his son, Toshi, and his grandson, Jack.
- 1. Nomura, M. (2011) Journey of a molecular biologist. Ann. Rev. Biochem. 80, 16 – 40.
- 2. Hosokawa, K., Fujimura, R.K., and Nomura, M. (1966) Reconstitution of functionally active ribosomes from inactive subparticles and proteins. Proc. Natl. Acad. Sci. USA 55, 198 – 204.
- 3. Guthrie, C. and Nomura, M. (1968) Initiation of protein synthesis: a critical test of the 30S subunit model. Nature 219, 232 – 235.
- 4. Traub, P. and Nomura M. (1968) Structure and function of E. coli ribosomes. V. Reconstitution of functionally active 30S ribosomal particles from RNA and proteins. Proc. Natl. Acad. Sci. USA 59, 777 – 784.
- 5. Nomura, M. and Erdmann, V.A. (1970) Reconstitution of 50S ribosomal subunits from dissociated molecular components. Nature 228, 744 – 748.
- 6. Yates, J.L., Arfsten, A.E., and Nomura M. (1980) In vitro expression of Escherichia coli ribosomal protein genes: autogenous inhibition of translation. Proc. Natl. Acad. Sci. USA 77, 1837 – 1841.
Millard Susman (email@example.com) is professor emeritus of genetics at the University of Wisconsin–Madison.