Sidney Altman, who paved the way for messenger RNA, is no more

American-Canadian scientist Sidney Altman, joint winner of the 1989 Nobel Prize in Chemistry for his discoveries on RNA, which is at the heart of two vaccines against COVID-19, died on April 5. He would have celebrated his 83e birthday in a month.

The scientific community is in mourning — and particularly at the Montreal Clinical Research Institute (IRCM) and the Department of Biochemistry and Molecular Medicine of the University of Montreal, which had recently welcomed this eminent researcher as professor in residence and visiting professor. .

Born in 1939 in the Montreal district of Notre-Dame-de-Grâce to parents from Eastern Europe, Sidney Altman did his university studies in the United States, first at the Massachusetts Institute of Technology (MIT) in Boston, where he completed a bachelor’s degree in physics, then at the University of Colorado, where he obtained a doctorate in molecular biology.

He will then carry out a first postdoctoral internship at Harvard University, then a second at the University of Cambridge, in England, within the group of Francis Crick, co-discoverer of the structure of DNA. “It was there that he had his first intuitions about the possible functions of RNA”, ribonucleic acid, emphasizes Jean-François Côté, president and interim scientific director of the IRCM.

A close friend of Mr. Altman, the former director of the IRCM Michel Chrétien relates that he then tried “to obtain a position in a Canadian university, but that he did not find one”.

He was eventually hired by Yale University, Connecticut, where he remained until his death, “offering to pursue RNA research, which was pretty bold, because up until then people believed than messenger RNA [ARNm] was only a copy of DNA and that this molecule did not deserve our interest,” says Mr. Côté. “And for this reason, it was a big challenge to obtain initial financing,” he underlines.

against dogma

Remember that during the production of a protein, the DNA sequence which encodes it is first copied in the form of messenger RNA (mRNA). Small molecules of transfer RNA (tRNA), corresponding to triads of nucleotides (basic constituents of DNA), are also generated. These small segments of tRNA are then used to decode the mRNA and transmit its information to the cell so that it synthesizes the protein in question.

Dr. Altman knew that tRNA was produced in an inactive form and that a small piece of its sequence had to be cleaved by an enzyme for these molecules to become functional. “The dogma at the time was that all enzymes were proteins. During 10 years, [Sidney Altman] looked for the protein that cleaved the tRNA, and he finally realized that it was not a protein, but the RNA itself that carried out this enzymatic activity,” explains Dr.r Chrétien.

“He had a lot of trouble getting this discovery accepted, because it went against dogma. But he had convincing chemical evidence, which was further confirmed by Thomas Cech, another American who was working on the same problem, but with a different approach. This evidence was such that it allowed Altman and Cech to obtain the Nobel Prize in Chemistry in 1989,” he continues.

“This discovery was also revolutionary [parce qu’en mettant en évidence le rôle primordial de ces ARN catalytiques dans la synthèse des protéines]it called into question the hypothesis put forward to explain the origin of life ”, maintains the Dr Chrétien.

Montrealers at heart

The latter is also very saddened by the death of his great friend. “His attachment to Montreal immediately brought us closer. And we also shared scientific ideas, because I have been working since 1967 on proteins that also need enzymatic cleavage to become active! »

“Dr. Altman’s discovery has sparked a real interest in the study of RNA, which is now used in the development of vaccines and treatments. Seeing all the spin-offs from RNA research over the past 30 years, we realize that he was truly a visionary,” points out Jean-François Côté, also saddened to have lost this exceptional colleague.

As professor in residence at the IRCM, Sidney Altman brought his extensive expertise to the institute’s RNA research group last fall, explains Mr. Côté. “He gave a course by Zoom to students at the University of Montreal, he actively participated in our grant applications, and he was supposed to come and work in Montreal with us for a few months a year, but unfortunately illness took him away. carried away. »

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