Ribozymes and Catalytic RNA

RNA molecules that act as enzymes — from self-splicing introns to the ribosome — and what their existence implies for the origin of life.

Definition

Ribozymes are RNA molecules that catalyse specific biochemical reactions; catalytic RNA is the broader phenomenon of RNA-based catalysis, in which a folded RNA active site, rather than a protein, accelerates a reaction such as RNA cleavage, ligation, or peptide bond formation.

Scope

This topic covers RNA-catalysed reactions and the molecules that perform them: self-splicing group I and II introns, the RNA component of RNase P, small self-cleaving ribozymes, and the ribosome as the prime example of a natural ribozyme. It addresses how folded RNA active sites achieve catalysis and the bearing of catalytic RNA on the RNA world hypothesis. The general biology of RNA structure is covered in a companion topic.

Core questions

• How can an RNA molecule catalyse a chemical reaction?
• What kinds of reactions do natural ribozymes carry out?
• Why is the ribosome considered a ribozyme?
• What does catalytic RNA imply about the early evolution of life?

Key theories

RNA can be an enzyme

Cech's demonstration that a Tetrahymena intron excises itself without protein established that RNA can fold into an active site and catalyse a reaction, overturning the assumption that all enzymes are proteins.

RNA world implication

Because RNA can both store information and catalyse reactions, including peptide bond formation in the ribosome, catalytic RNA supports the hypothesis that an RNA-based metabolism preceded DNA and protein enzymes.

Mechanisms

A ribozyme folds into a precise tertiary structure that positions reactive groups and often coordinates metal ions to stabilise transition states, much as a protein enzyme does. Self-splicing introns catalyse their own excision through transesterification reactions; the RNA subunit of RNase P cleaves precursor transfer RNAs; small self-cleaving ribozymes sever their own backbone; and the ribosome's RNA catalyses peptide bond formation. In each case the catalytic power resides in the folded RNA itself, sometimes assisted by associated proteins.

Clinical relevance

Engineered ribozymes and the ribozyme nature of the ribosome inform RNA-targeted research tools and antibiotic action; offered as significance, not clinical guidance.

History

Cech's 1982 report of self-splicing RNA and Altman's parallel work on the catalytic RNA of RNase P established catalytic RNA, recognised by the 1989 Nobel Prize in Chemistry; later structural work showing the ribosome to be a ribozyme cemented RNA's catalytic importance.

Key figures

• Thomas Cech
• Sidney Altman
• Harry Noller

Seminal works

• kruger1982
• watson2013

Frequently asked questions

What is a ribozyme?

An RNA molecule that acts as an enzyme, using its folded structure to catalyse a chemical reaction such as cutting or joining RNA.

Why does catalytic RNA matter for the origin of life?

It shows that one kind of molecule can both carry information and catalyse reactions, making an early RNA-based life plausible before DNA and proteins existed.