Background

In the late 1950's, after discovering the structure and function of DNA as genetic material, Francis Crick formulated the so-called "central dogma of molecular biology": DNA makes RNA makes protein (Fig. 1). According to this idea, information always flows from DNA as the genetic material through RNA as the messenger to protein as the carrier of catalytic function. However, thought-provoking discoveries in the early 1970's by Howard Temin and David Baltimore (Nobel Prize for Medicine 1975) showed that some viruses, the so-called retroviruses, use RNA as their genetic material. These viruses, one of which is HIV, manage to insert themselves into the host's DNA genome after reverse-transcribing their genomic RNA into DNA, utilizing enzymes termed reverse transcriptases, RTases.

The early 1980's then saw another pioneering discovery by Tom Cech and Sidney Altman (Nobel Prize for Chemistry in 1989). Certain RNA's actually carry catalytic function as previously only proteins were believed to be able to. That makes these catalytic RNA's, or ribozymes, the only biomolecules that can do it all; Store genetic information in their sequence, carry this message around, and execute a catalytic function to chemically modify a substrate. These discoveries shattered the central dogma of molecular biology (see figure 1 above) and sparked intensive research to unravel the mystery of how RNA can accomplish these diverse tasks.

One fascinating consequence of RNA having both genetic and catalytic function is that one can imagine an "RNA world" as the origin of all life on earth. A small RNA genome could have acquired catalytic activity to make error-prone copies of itself that undergo a natural selection for the fastest replicating RNA. The fastest replicator then could have started acquiring additional catalytic activities to develop its own metabolism, creating the first primitive life form.

Any questions or comments? Please email Nils G. Walter.

Experimental Techniques