Letters to Nature

Nature 402, 323-325 (18 November 1999) | doi:10.1038/46335; Received 17 May 1999; Accepted 13 September 1999

A ribozyme that lacks cytidine

Jeff Rogers & Gerald F. Joyce

  1. Departments of Chemistry and Molecular Biology, and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA

Correspondence to: Gerald F. Joyce Correspondence and requests for materials should be addressed to G.F.J. (e-mail: Email: gjoyce@scripps.edu).

The RNA-world hypothesis proposes that, before the advent of DNA and protein, life was based on RNA, with RNA serving as both the repository of genetic information and the chief agent of catalytic function1. An argument against an RNA world is that the components of RNA lack the chemical diversity necessary to sustain life. Unlike proteins, which contain 20 different amino-acid subunits, nucleic acids are composed of only four subunits which have very similar chemical properties. Yet RNA is capable of a broad range of catalytic functions2, 3, 4, 5, 6, 7. Here we show that even three nucleic-acid subunits are sufficient to provide a substantial increase in the catalytic rate. Starting from a molecule that contained roughly equal proportions of all four nucleosides, we used in vitro evolution to obtain an RNA ligase ribozyme that lacks cytidine. This ribozyme folds into a defined structure and has a catalytic rate that is about 105-fold faster than the uncatalysed rate of template-directed RNA ligation.