Classic Study Maps How Retroviral Enzymes Read RNA Versus DNA Templates

Baltimore and Smoler, publishing in Proceedings of the National Academy of Sciences in 1971, examined how the DNA-making enzyme found inside RNA tumor viruses chooses its templates and starting material.

Working with purified virus particles from two well-known animal viruses, avian myeloblastosis virus and mouse leukemia virus, the researchers tested how each virus's DNA polymerase — an enzyme that builds new DNA strands — behaves when supplied with different synthetic nucleic acid chains. They found that single-stranded RNA chains built from a repeating single letter code (homoribopolymers) worked efficiently as templates, but only once a short matching DNA starter piece, called a primer, was added. The enzyme then built a new DNA strand until it matched the length of the RNA template. The two viruses showed slightly different preferences among the four possible RNA building blocks tested.

By contrast, when the same DNA-building chains (polydeoxyribonucleotides) were offered as templates instead of RNA, the enzyme mostly failed to make any new DNA at all. The authors conclude these viral enzymes need a primer like other DNA polymerases, but are unusual in strongly preferring RNA templates over DNA ones. The study used only synthetic, repetitive nucleic acids in a test-tube system, so it cannot say how the enzyme behaves with natural, complex genetic sequences or inside a living cell.