How to Kinetically Dissect an RNA Machine

RNA-based machines are ubiquitous in Nature and increasingly important for medicines. They fold into complex, dynamic structures that process information and catalyze reactions, including reactions that generate new RNAs and proteins across biology. What are the experimental strategies and steps that are necessary to understand how these complex machines work? Two 1990 papers from Herschlag and Cech on “Catalysis of RNA Cleavage by the Tetrahymena thermophila Ribozyme” provide a master class in dissecting an RNA machine through kinetics approaches. By showing how to propose a kinetic framework, fill in the numbers, do cross-checks, and make comparisons across mutants and different RNA systems, the papers illustrate how to take a mechanistic approach and distill the results into general insights that are difficult to attain through other means.