Multiple translational products from a five-nucleotide ribozyme.

The authors have discovered that their previously selected self-aminoacylating ribozyme has just 5 essential nucleotides. The 5-mer ribozyme catalyzes the aminoacylation of external substrates and subsequent peptide-bond formation of activated amino acids. This finding significantly fine tunes our understanding of ribozyme size requirements.

The RNA World hypothesis describes a time during the origins of life during which RNA molecules performed all catalytic and informational processes. A sticking point with this hypothesis is the source of the ribozymes, as many modern RNA enzymes are over 100 nucleotides in length and it can be difficult to think outside the paradigm of modern biology, even when considering the origins of life. Random polymerization of 100-mer RNAs, while possible, requires an abundance of activated RNA monomers. Furthermore, sampling the entire 100-mer RNA sequence space (4^100 different possible sequences) would appear to be intractable. Thus, the discovery of smaller ribozymes is important to progress in prebiotic chemistry. In extant biology, too, there has been a strong underestimation of the roles of small RNA molecules. For example, it was only recently discovered that the ~22-nucleotide RNA molecules (miRNAs) abundant in cells actually play a critical role in gene expression rather than simply being non-functional degradation products of larger cellular RNAs. Turk et al. have demonstrated that their 5-nucleotide ribozyme is capable of aminoacylating a 4-nucleotide substrate, meaning that the entire active site is composed entirely of only 9 nucleotides. This raises the question: how many other ribozyme functionalities can be contained within a 9-nucleotide active site? The answer to this question will surely impact our understanding of the plausibility of the RNA World hypothesis, but may also have implications for biology today.