RNA-based enzyme synthesizes various RNA structures

The ability to produce many types of RNA molecules without the help of protein enzymes would have been necessary if early forms of life were based on RNA, which is a popular hypothesis. Gerald F. Joyce and David P. Horning of Scripps Research Institute, in La Jolla, Calif., have now identified a ribozyme—an RNA-based enzyme—that can replicate a wide variety of RNA molecules and can even catalyze an all-RNA version of the polymerase chain reaction (PCR) used to amplify genetic material (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1610103113). The ribozyme was singled out after 24 rounds of in vitro evolution starting from an engineered form of the class I polymerase ribozyme. In each round of evolution, ribozymes were selected for their ability to synthesize ligand-binding RNA molecules called aptamers from complementary RNA templates. The evolved ribozyme synthesizes RNA molecules about 100 times as fast as the starting ribozyme and is able to synthesize sequences that stymie the original one. The evolved ribozyme synthesized a variety of highly structured RNA molecules with different functions, including aptamers, other ribozymes, and transfer RNA, the kind of RNA used in protein synthesis. The evolved enzyme is even able to exponentially amplify short RNA templates, albeit at low yields, in an RNA-only version of PCR.