DNA Transcription and tRNA Ligase: the Work of John Abelson

Abstract

Saccharomyces cerevisiae tRNA Ligase. Purification of the Protein and Isolation of the Structural Gene(Phizicky, E. M., Schwartz, R. C., and Abelson, J. (1986) J. Biol. Chem. 261, 2978–2986)Yeast RNA Ligase Mutants Are Nonviable and Accumulate tRNA Splicing Intermediates(Phizicky, E. M., Consaul, S. A., Nehrke, K. W., and Abelson, J. (1992) J. Biol. Chem. 267, 4577–4582) Saccharomyces cerevisiae tRNA Ligase. Purification of the Protein and Isolation of the Structural Gene (Phizicky, E. M., Schwartz, R. C., and Abelson, J. (1986) J. Biol. Chem. 261, 2978–2986) Yeast RNA Ligase Mutants Are Nonviable and Accumulate tRNA Splicing Intermediates (Phizicky, E. M., Consaul, S. A., Nehrke, K. W., and Abelson, J. (1992) J. Biol. Chem. 267, 4577–4582) John Norman Abelson was born in Grand Coulee Dam, Washington, in 1938. He attended Washington State University and graduated in 1960 with a bachelor's degree in physics. He then moved east to pursue graduate studies at Johns Hopkins University, where he earned a doctorate in biophysics in 1965. After that, Abelson moved again, this time to Cambridge, England, to do a postdoctoral fellowship in the Structural Studies Division at the MRC Laboratory of Molecular Biology. There he worked with Sydney Brenner and Francis Crick studying DNA transcription. In 1968, Abelson returned to the United States to accept a position as assistant professor in the chemistry department at the University of California, San Diego. He was promoted to associate professor in 1973 and professor in 1977. In 1982, Abelson joined the faculty of the California Institute of Technology as a professor of biology. He chaired the Division of Biology and became the George Beadle Professor of Biology in 1991. At Caltech Abelson continued to study transcription, focusing on tRNA precursor splicing and intron excision. In the early 1980s he was able to partially purify tRNA ligase from Saccharomyces cerevisiae (1Greer C.L. Peebles C.L. Gegenheimer P. Abelson J. Mechanism of action of a yeast RNA ligase in tRNA splicing..Cell. 1983; 32: 537-546Abstract Full Text PDF PubMed Scopus (178) Google Scholar). A few years later, he and his colleagues purified the protein to near homogeneity, which is the subject of the first Journal of Biological Chemistry (JBC) Classic reprinted here. Using affinity elution chromatography, they showed that tRNA ligase is a single polypeptide of 90 kDa that also contains polynucleotide kinase and 2′,3′-cyclic phosphate 3′-phosphodiesterase activities. They also determined the amino-terminal sequence of the purified protein and used this information to isolate the gene encoding tRNA ligase by hybridization of an appropriate set of mixed oligonucleotides to a library of yeast DNA. In the second JBC Classic reprinted here, Abelson and his colleagues continue their ligase studies, demonstrating that not only is tRNA ligase critical for tRNA splicing in the yeast cell, but it is also essential for cellular survival. They created a haploid yeast strain carrying a chromosomal deletion of the ligase gene and found that it was viable only if ligase protein was supplied from a plasmid copy of the gene. When synthesis of the plasmid-borne ligase was repressed, the cells accumulated endonuclease-cut, unligated half-molecules and eventually died. Two temperature-sensitive ligase mutant yeast strains also accumulated unligated half-molecules at nonpermissive temperatures. Abelson retired in 2002 and is currently George W. Beadle Professor of Biology, Emeritus at Caltech. He is also president and executive director of Agouron Institute, a non-profit research foundation, which he co-founded in 1978. Abelson also participated in the creation of Agouron Pharmaceuticals, Inc., a small San Diego firm that used rational drug design to develop Viracept, the leading drug used for controlling HIV infections. In recognition of his contributions to science, Abelson has received many awards and honors including the Washington State University (WSU) Distinguished Alumnus Award from the College of Sciences (1993), the WSU Alumni Achievement Award (1995), and the WSU Regents' Distinguished Alumnus Award (2004), as well as election to the National Academy of Sciences (1985), the American Academy of Arts and Sciences (1985), and the American Philosophical Society (2001). He has served as an editor of Methods in Enzymology for the past 15 years and was an assistant editor for Analytical Biochemistry (1980–1987) and a member of the JBC editorial board. He is also a past president of the RNA Society.