Sterling Professor of Molecular Cellular and Developmental Biology
Professor of Chemistry, Yale University

Sidney Altman’s research career began with a study of acridine-induced damage of bacteriophage T4 DNA, the organism in which a study of acridine-induced mutations by Crick and co-workers led to the elucidation of the triplet nature of the genetic code. Altman showed that, at mutagenic concentrations, acridines lead to the production of low molecular weight (broken) T4 DNA. Subsequently, Altman identified a T4-encoded DNA endonuclease, an enzyme that most likely plays a role in phage recombination. Dr. Altman’s research interests then shifted to acridine-induced mutations in E. coli tRNA. This work led to the first identification of a radioactively pure tRNA precursor species and laid the basis for further work on the RNA processing enzyme, ribonuclease P.

Ribonuclease P (RNase P) was readily identified in crude extracts of bacteria using the newly found tRNA precursor as a substrate. The enzyme removes the “extra” upstream leader sequence from the precursor molecule with a single endonucleolytic event at the beginning of the mature tRNA species. One species of RNase P is responsible for processing all tRNA precursors (as well as several other small, stable RNAs in E. coli). The enzyme is ubiquitous and essential. In eukaryotes, the enzyme is found in both nuclei and mitochondria.

Altman’s lab showed that in eubacteria RNase P is composed of one RNA and one protein subunit. A few years after this demonstration, and that of the essentiality of the RNA subunit for function of the enzyme, it was shown that the RNA subunit is the catalytic component of the enzyme. This finding altered thinking about the nature of biological catalysts and stimulated speculation about some of the important steps in the origin of life on earth. Surprisingly, the general biochemical nature of RNase P in eukaryotes is different from that in prokaryotes. In the nuclei of eukaryotes, the enzyme also has an RNA subunit , which is not catalytic alone, and also has nine or more protein subunits. The function of these subunits is currently under investigation.

As an outgrowth of studies on the the essential features of substrates for RNase P, a general method has been developed to inactivate the expression of any targeted gene in any organism. To date, the efficacy of this method has been demonstrated in laboratory cultures of E. coli and human tissue culture cells. For example, the drug resistant phentoype of E. coli can be reversed using this technology and influenza virus infection of mouse cells can be completely blocked.

Altman has been chair of his department at Yale and Dean of Yale College. He is a member of the National Academy of Sciences, the American Philosophical Society and a Nobel Laureate in Chemistry (1989).

He received bachelor of science degrees in chemistry and biochemistry from the University of California at San Diego in 1979 and a doctorate degree in chemistry from Colorado State University in 1984. Upon completion of an NIH postdoctoral fellowship at Harvard University in 1986, was a faculty member in the Department of Chemistry and Biochemistry at the University of California at Los Angeles, where he remains an adjunct faculty member.