riboenzymes

Riboenzymes, or ribozymes, are RNA molecules that function as enzymes, catalyzing specific chemical reactions without the need for protein catalysts. Their catalytic activity arises from their folded three-dimensional structure, which positions substrates and often employs divalent metal ions such as magnesium to facilitate catalysis. Reactions include RNA cleavage, ligation, and nucleotide modification, as well as self-splicing and processing of RNA precursors.

The concept emerged in the 1980s from seminal experiments showing RNA-based catalysis. Thomas Cech and colleagues demonstrated self-splicing introns in Tetrahymena, proving that RNA can act as an enzyme. Independently, Sidney Altman’s work on RNase P revealed an RNA component capable of catalyzing tRNA processing. The discoveries revolutionized views of biology and earned them a shared Nobel Prize in 1989.

Representative examples include Group I and Group II introns, which can splice themselves out of RNA transcripts; hammerhead and hairpin ribozymes, which catalyze site-specific RNA cleavage; and the RNase P ribozyme, which processes precursor tRNA. The ribosome is also a ribozyme, with its catalytic peptidyl transferase center formed by ribosomal RNA. Additionally, the glmS ribozyme acts as a metabolite-activated regulator in bacteria, cleaving itself in response to a small molecule.

Ribozyme activity can be studied and harnessed in vitro and in vivo, and researchers can engineer ribozymes through in vitro selection and rational design to perform novel reactions. Their study informs theories about the RNA world and the evolution of enzymatic function, demonstrating that RNA can serve as both genetic material and a catalyst.

Applications range from molecular biology tools for RNA processing and gene regulation to potential therapeutic approaches, though achieving efficient delivery and specificity in living systems remains a challenge.

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