Sidney Altman - Career

Career

After receiving his Ph.D., Altman embarked upon the first of two research fellowships. He joined Matthew Meselson's laboratory at Harvard University to study a DNA endonuclease involved in the replication and recombination of T4 DNA. Later, at the MRC Laboratory of Molecular Biology in Cambridge, England, Altman started the work that led to the discovery of RNase P and the enzymatic properties of the RNA subunit of that enzyme. John D. Smith, as well as several post-doctoral colleagues, provided Altman with very good advice that enabled him to test his ideas. "The discovery of the first radiochemically pure precursor to a tRNA molecule enabled me to get a job as an assistant professor at Yale University in 1971, a difficult time to get any job at all."

Altman's career at Yale followed a standard academic pattern with promotion through the ranks until he became Professor in 1980. He was Chairman of his department from 1983–1985 and in 1985 became the Dean of Yale College for four years. On July 1, 1989 he returned to the post of Professor on a full-time basis.

While at Yale, Altman's Nobel Prize work came with the analysis of the catalytic properties of the ribozyme RNase P. RNase P is a ribonucleoprotein particle consisting of both a structural RNA molecule and one (in prokaryotes) or more (in eukaryotes) proteins. Originally, it was believed that, in the bacterial RNase P complex, the protein subunit was responsible for the catalytic activity of the complex, which is involved in the maturation of tRNAs. During experiments in which the complex was reconstituted in test tubes, Altman and his group discovered that the RNA component, in isolation, was sufficient for the observed catalytic activity of the enzyme, indicating that the RNA itself had catalytic properties, which was the discovery that earned him the Nobel prize. Although the RNase P complex also exists in eukaryotic organisms, his later work revealed that in those organisms, the protein subunits of the complex are essential to the catalytic activity, in contrast to the bacterial RNase P.