Ribozymes

Ribozymes are RNA molecules that catalyze chemical reactions. Unlike most RNAs, which primarily serve in information transfer or structural roles, ribozymes possess intrinsic catalytic activity and can accelerate reactions such as RNA cleavage and ligation.

Ribozymes were discovered in the 1980s, notably by Thomas Cech and colleagues, who showed that the Tetrahymena self-splicing intron can remove itself from RNA transcripts without protein help. Independently, Sidney Altman and collaborators demonstrated that RNA components of RNase P catalyze tRNA maturation. These findings revealed that RNA can function as an enzyme and led to the identification of several catalytic RNA motifs, including self-splicing group I and II introns and small ribozymes such as hammerhead and hairpin ribozymes.

Ribozymes fold into compact three-dimensional structures that position reactive groups for catalysis. Many require divalent metal ions, particularly magnesium, which can participate directly in the chemical reaction or help stabilize the active fold. Catalysis often involves metal-ion mechanisms alongside general acid-base catalysis by RNA nucleotides themselves. Reactions include RNA cleavage, ligation, and the processing or maturation of RNA.

Examples include the hammerhead and hairpin ribozymes, the glmS ribozyme, and the catalytic core of the ribosome, whose peptidyl transferase activity is RNA-based. Beyond natural examples, ribozymes have been engineered for biotechnology and medicine, used in in vitro selection to evolve new activities, and explored as tools for gene regulation and therapeutic intervention.

Ribozymes illuminate RNA’s versatility and have been influential in discussions of the RNA world hypothesis, illustrating that RNA can both store genetic information and catalyze chemical transformations.