Finding aptamers and small ribozymes in unexpected places.

The discovery of the catalytic properties of RNAs was a milestone for our view of how life emerged and forced us to reformulate many of our dogmas. The urge to grasp the whole spectrum of potential activities of RNA molecules stimulated two decades of fervent research resulting in a deep understanding of RNA-based phenomena. Most ribozymes were discovered by serendipity during the analysis of chemical processes, whereas RNA aptamers were identified through meticulous design and selection even before their discovery in nature. The desire to obtain aptamers led to the development of sophisticated technology and the design of efficient strategies. With the new notion that transcriptomes cover a major part of genomes and determine the identity of cells, it is reasonable to speculate that many more aptamers and ribozymes are awaiting their discovery in unexpected places. Now, in the genomic era with the development of powerful bioinformatics and sequencing methods, we are overwhelmed with tools for studying the genomes of all living and possibly even extinct organisms. Genomic SELEX (systematic evolution of ligands by exponential enrichment) coupled with deep sequencing and sophisticated computational analysis not only gives access to unexplored parts of sequenced genomes but also allows screening metagenomes in an unbiased manner.