RESEARCH N a t u r a l R N A , b e c a u s e it i s p o l y m e r ized f r o m four nucleotides, i s c o m p l e x , difficult t o w o r k w i t h
But a v a i l a b i l i t y of "synthetic R N A s composed o f a single nucleotide provides scientists with simpler, k n o w n , a n d e a s i e r - t o - w o r k - w i t h substances
Probing the Cell From easily synthesized compounds resembling nucleic acids w e learn more about heredity, cancer XTROTEIN SYNTHESIS, cancer, heredity—
t h e key to these and perhaps other biological problems may lie in the structure a n d function of ribonucleic acid (RNA) a n d deoxyribonucleic acid ( D N A ) . Better understanding of these problems may one day come from research at New York University. There, Severo Ochoa, with a half dozen colleagues, synthesizes RNA-like compounds from materials readily obtained from yeast or animal tissues. Because the n e w compounds are simpler than native RNA and are of known composition, they are easier to work with. Ochoa has been interested in enzymes in biological oxidation and synthesis since his studies a t University of Madrid. I n early 1954, he and Marianne Grunberg-Manago isolated a new enzyme, polynucleotide phosphorylase, from Azotobacter vinelandii. In studying this enzyme, Ochoa discovered that it can catalyze synthesis of RNA-like compounds. 24
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• Making a Molecule. RNA a p p e a r s to b e a n unbranched chain polymer of nucleotides; each nucleotide consists of phosphoric acid, a sugar (D-ribose), and one of four nitrogeneous bases (adenine, uracil, guanine, or cytosine). Each nucleotide h a s a molecular weight of a few h u n d r e d . D e p e n d ing on where it comes from a n d h o w it's made, RNA polymerized from these nucleotides can have a molecular weight as high a s 1 million. Ochoa's enzyme acts on a simple nucleotide, o'-nucleoside diphosphate, splitting off one of the phosphoric groups: Base-ribose-P-P-*
Base-ribose-P-{-P
At the same time, this product polymerizes with similar units: Base-ribose-P
I
Base-ribose-P
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Base-ribose-P
Natural R N A m a d e b y cells is a copolymer witli all four bases. But by acting on a. nucleotide with only one base, the enzyme makes not a copolymer, but a polymer with only one base. For some t i m e , Ochoa felt his polynucleotides w e r e closely related to natural RNA. After a year's research, he says some o£ the polynucleotides a r e the s a m e as n a t u r a l R J N A :
• Molecular w e i g h t s are the same. • Biological activities a r e t h e same. • Most important, RNA m a d e by Azotobacter itself is indistinguishable from that m a d e by t h e e n z y m e acting on all four naturally occurring nucleoside diphosphates. Certain that his polynucleotides are closely related to RNA, Ochoa is broadening his work. F o r one thing, he wants to isolate a purer enzyme; then he c a n get a better idea of how the polymers are m a d e . O n c e polynucleotides a r e made, next question is, " W h a t a r e they?" R. C. Warner directs the study of this problem. Using s u c h t e c h n i q u e s as electrophoresis, ultraviolet absorption, and ultracentrifuge, he hopes to relate chemical and physical properties to
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