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13 Building a Catalytic Active Site Using Only RNA

Thomas R. Cech, Barbara L. Golden


Two of the most fundamental requirements for life are information storage and catalytic function. Without storage, transfer, and replication of information, a system cannot learn from its past and improve its viability; that is, there can be no natural selection. Equally essential to life is catalytic (enzymatic) function. At the very least, there must be machinery to catalyze the copying of the informational molecules. This process must proceed with considerable fidelity, yet some frequency of errors is also necessary to provide the diversity that allows adaptation and evolution. Beyond replication of the genome, additional catalytic functions would be highly advantageous to provide basic metabolism for even a primitive self-reproducing system.

In contemporary organisms information is stored in the form of DNA. However, the persistence of RNA genomes in many viruses shows us that this sister nucleic acid is competent for information storage, at least for small genomes. Biocatalytic function in the modern world is mostly the domain of protein enzymes, although ribonucleoproteins (RNPs) still catalyze the essential cellular reactions of protein synthesis and RNA splicing. By what evolutionary pathway did this DNA-RNA-protein solution to the problem of life come about? The finding that RNA, an informational molecule, can by itself catalyze biochemical reactions has rekindled enthusiasm for the possibility that a key intermediate stage was an RNA World, with RNA providing both information and function, genotype and phenotype.

One version of this RNA World hypothesis is diagrammed in Figure 1. RNA...

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