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Furth et al. 237 (8): 2611

J. Biol. Chem., Vol. 281, Issue 15, 12, April 14, 2006
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The Discovery and Isolation of RNA Polymerase by Jerard Hurwitz

Nicole Kresge, Robert D. Simoni, and Robert L. Hill

The Role of Deoxyribonucleic Acid in Ribonucleic Acid Synthesis. I. The Purification and Properties of Ribonucleic Acid Polymerase
(Furth, J. J., Hurwitz, J., and Anders, M. (1962) J. Biol. Chem. 237, 2611–2619)

Jerard Hurwitz was born in New York City in 1928. He attended Indiana University and earned a B.A. in Chemistry in 1949. He then went on to Western Reserve University where he studied the enzymatic phosphorylation of vitamin B6 derivatives and their function as coenzymes. He received his Ph.D. in Biochemistry in 1953 and spent the next year working in Albert Neuberger's laboratory at the National Medical Research Council in London, England. Upon returning to the United States, Hurwitz went to Bethesda, Maryland, where he did a postdoctoral fellowship with Bernard Horecker at the National Institutes of Health. At that time, Horecker was studying the enzymes involved in the oxidation of 6-phosphogluconate and the metabolic intermediates formed in the pentose phosphate pathway, as mentioned in a previous Journal of Biological Chemistry (JBC) Classic (1), and Hurwitz joined in this research. While working with Horecker, he isolated and characterized a number of enzymes and substrates that firmly established the photosynthetic CO2 fixation cycle proposed by Melvin Calvin.

In 1956, Hurwitz joined the microbiology department at Washington University in St. Louis, Missouri. He remained there for 2 years, during which he investigated the incorporation of ribonucleotides into RNA. He then moved back to New York to become an Assistant Professor of Microbiology at the New York University (NYU) School of Medicine. He was promoted to Associate Professor in 1960. Influenced by the work he carried out in St. Louis, Hurwitz decided to focus on RNA synthesis in his laboratory at NYU.

Hurwitz was not the first person to study the enzymes involved in RNA synthesis. In 1955, Marianne Grunberg-Manago and Severo Ochoa, who was the author of a previous JBC Classic (2), reported the isolation of an enzyme that catalyzed the synthesis of RNA. Initially Ochoa hoped this enzyme, named polynucleotide phosphorylase, might be responsible for the biosynthesis of RNA. However, the realization that polynucleotide phosphorylase did not need a DNA template for RNA synthesis dispelled this idea, and it was subsequently determined that the function of polynucleotide phosphorylase was to degrade RNA, not synthesize it, despite the fact that the enzyme runs its natural reaction in reverse in vitro.

Undeterred by Ochoa's findings, Hurwitz started his search for RNA polymerase in 1959, using Escherichia coli extracts. That same year, Samuel B. Weiss reported that rat liver nuclei supported RNA synthesis in reaction mixtures containing all four rNTPs (3). Hurwitz continued his experiments, and by 1960 he reproducibly demonstrated a marked stimulation of RNA synthesis by externally added DNA in his E. coli preparations. He published a note in Biochemical and Biophysical Research Communications describing his findings (4). To his surprise, in the same issue of the journal, Audrey Stevens reported that extracts of E. coli incorporated labeled ATP into RNA in a reaction requiring all four rNTPs (5). Later that year James Bonner, who was also the author of a JBC Classic (6), reported similar findings with extracts of peas (7). Thus, four different laboratories had simultaneously discovered RNA polymerase.Go


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  		Jerard Hurwitz. Photograph courtesy of the Memorial Sloan-Kettering Cancer Center.

 
After its initial discovery, Hurwitz continued to focus on RNA polymerase. In collaboration with John J. Furth, who joined Hurwitz's lab as a postdoctoral fellow, Hurwitz purified RNA polymerase. This is the subject of the JBC Classic reprinted here. Using two different techniques, Hurwitz, Furth, and Monika Anders purified the enzyme 300-fold from E. coli extracts. Their purified RNA polymerase catalyzed the synthesis of RNA from ribonucleoside triphosphates of adenine, uracil, guanine, and cytosine and required the presence of DNA and Mn2+ or Mg2+. Hurwitz also noted that the RNA formed is a complementary copy of the priming DNA and suggested that RNA polymerase synthesizes an RNA involved in protein synthesis. More detailed information on Hurwitz's work on RNA polymerase can be found in his JBC Reflections (8).

In 1963, Hurwitz left NYU to become a Professor of Molecular Biology at Albert Einstein College of Medicine. He was Chairman of the Department of Developmental Biology from 1965 to 1984 and then joined the Sloan-Kettering Institute where he remains today. He served as vice-chairman of the Sloan-Kettering Institute from 1991 to 2003. Currently Hurwitz's laboratory is focused on eukaryotic DNA replication and its control, with emphasis on the identification of the protein components involved in these processes.

Hurwitz is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. His honors and awards are numerous and include the Eli Lilly Award in Biochemistry (1962), the Institut Pasteur Hazen Lectureship (1972), and the New York Academy of Science's Louis and Bert Freeman Foundation Prize for Research in Biochemistry (1982). Hurwitz has also served on several editorial boards including those of the Journal of Molecular Biology and the Journal of Bacteriology.1

FOOTNOTES

1 Biographical information on Jerard Hurwitz was taken from Ref. 8. Back


REFERENCES

  1. JBC Classics: Horecker, B. L., Smyrniotis, P. Z., and Seegmiller, J. E. (1951) J. Biol. Chem. 193, 383–396 (http://www.jbc.org/cgi/content/full/280/29/e26)
  2. JBC Classics: Stern, J. R., and Ochoa, S. (1951) J. Biol. Chem. 191, 161–172; Korkes, S., del Campillo, A., Gunsalus, I. C., and Ochoa, S. (1951) J. Biol. Chem. 193, 721–735 (http://www.jbc.org/cgi/content/full/280/11/e8)
  3. Weiss, S. B., and Gladstone, L. (1959) A mammalian system for the incorporation of cytidine triphosphate into ribonucleic acid. J. Am. Chem. Soc. 81, 4118[CrossRef]
  4. Hurwitz, J., Bresler, A., and Diringer, R. (1960) The enzymic incorporation of ribonucleotides into polyribonucleotides and the effect of DNA. Biochem. Biophys. Res. Commun. 3, 15–18
  5. Stevens, A. (1960) Incorporation of the adenine ribonucleotide into RNA by cell fractions from E. coli B. Biochem. Biophys. Res. Commun. 3, 92–96[CrossRef]
  6. JBC Classics: DeLange, R. J., Fambrough, D. M., Smith, E. L., and Bonner, J. J. (1969) J. Biol. Chem. 244, 5669–5679 (http://www.jbc.org/cgi/content/full/280/36/e33)
  7. Huang, R. C., Maheshwari, N., and Bonner, J. (1960) Enzymatic synthesis of RNA. Biochem. Biophys. Res. Commun. 3, 689–694[CrossRef][Medline] [Order article via Infotrieve]
  8. Hurwitz, J. (2005) The discovery of RNA polymerase. J. Biol. Chem. 280, 42477–42485[Free Full Text]

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