A few years before I started my graduate studies, Carl Woese was establishing a collaboration with his friend, colleague, and my PhD advisor, Harry Noller. Carl was introducing comparative methods to Harry's lab to determine the secondary structure for the 16S and 23S rRNAs. In addition to an experimental project that had minimal to no success, I was attempting to predict an RNA secondary structure from a single sequence. I determined after a few months that the complexity of RNA folding was much greater than ever anticipated. Ten lessons were learned about the dynamics of RNA folding, the comparative methods used to accurately predict the RNAs secondary structure and the beginnings of its tertiary structure, the use of comparative methods to reveal much more than ever anticipated about RNA structure, other applications beyond RNA structure, and the lessons about the process of scientific discovery.
Keywords: Carl Woese; RNA; RNA higher-order structure; RNA secondary structure; RNA structure principles; comparative analysis; covariation analysis.