1989 Nobel Prize in Chemistry

Reason for Award

for the discovery of the catalytic properties of RNA

Laureates

Sidney Altman
Sidney Altman

CanadaCanada, United States of AmericaUnited States of America

Thomas Robert Cech
Thomas Robert Cech

United States of AmericaUnited States of America

Explanation

In our body, proteins are built according to plans written in DNA. Mr. Altman and Mr. Cech discovered that a helper molecule called RNA can speed up chemical reactions all by itself. It’s like finding out that the messenger who delivers parts can also assemble the toy on arrival. This surprise gave scientists a brand-new clue about how life works.

Related Keywords

ribozyme

A ribozyme is an RNA molecule capable of catalyzing chemical transformations of itself or another substrate. Before their discovery enzymes were thought to be proteins only, but ribozymes broadened that definition. Natural examples include the ribosomal peptidyl-transferase center, the U6 RNA of the spliceosome, and hammerhead ribozymes in viral genomes. Many artificial ribozymes have been generated by SELEX and can catalyze reactions such as DNA cleavage or polymerization. Catalytic activity depends on intricate RNA folds and metal-ion binding, and applications are expanding in pharmacology and synthetic biology.

RNase P

RNase P is an essential endonuclease that removes the 5′ leader of precursor tRNA to yield mature tRNA. In bacteria it consists of an M1 RNA and a small protein subunit, yet the catalytic center resides in the RNA. Altman’s work proved Mg2+-dependent activity of the RNA alone, marking the starting point of the ribozyme concept. Homologs are conserved in archaea and eukaryotes, some containing multiple proteins that stabilize the RNA. Recent cryo-EM structures are revealing substrate-recognition pockets and transition-state stabilization strategies at atomic resolution.

self-splicing

Self-splicing is a reaction in which an intron excises itself and ligates the flanking exons without external factors. The Tetrahymena Group I intron described by Cech proceeds through a two-step phosphodiester transfer that uses an external GTP. Group II introns employ a lariat intermediate and are thought to be precursors of the eukaryotic spliceosome. Self-splicing contributes to genome plasticity and the spread of mobile elements, driving gene evolution. Engineered introns are being explored as molecular sensors and sequence-specific cleavage tools.

RNA world hypothesis

The RNA world hypothesis posits that early life relied on RNA to store genetic information and perform catalysis. The discovery of ribozymes provided key molecular evidence for this scenario. Laboratory evolution has produced self-replicating ribozymes and RNA polymerase ribozymes, aiming to recreate primitive genetic systems. Geochemical questions remain, such as spontaneous ribonucleotide synthesis and co-encapsulation with lipid membranes. The RNA world concept feeds into the later division of labor where DNA became the main information storage and proteins the versatile catalysts.

phosphodiester bond

The phosphodiester bond links the 3′ and 5′ carbons of the nucleic-acid backbone in DNA and RNA. Many ribozyme reactions catalyze cleavage or transfer of this bond. Cleavage often proceeds through a 2′,3′-cyclic phosphate intermediate or a pentacoordinate phosphorous transition state, with metal ions neutralizing charge and accelerating the reaction. The bond’s chemical stability is essential for preserving genetic information, yet reversible cleavage underlies RNA processing and DNA repair. In vitro the bond can be manipulated by nucleases or chemical reagents, forming the foundation of molecular biology techniques.

divalent metal ion catalysis

Divalent metal ion catalysis involves Mg2+ or Mn2+ neutralizing the negative phosphate backbone and stabilizing the transition state to accelerate reactions. Many ribozymes and the ribosome employ this strategy, sometimes using metal-bound water as the nucleophile. Ion positioning is crucial for RNA folding, and coordination geometry or ion selectivity strongly affects activity. Conservation of metal-binding motifs aids functional prediction and evolutionary analysis. Metal-dependent ribozymes are also being explored as ion sensors and catalysts for environmental remediation.

Tetrahymena thermophila

Tetrahymena thermophila is a ciliated unicellular eukaryote famous for discoveries such as nuclear dimorphism and telomerase activity. The rRNA gene intron studied by Cech resides in the macronuclear DNA of this organism and self-splices under mild conditions. Enzymes from Tetrahymena are often thermotolerant, making them suitable for ribozyme assays. Genome sequencing has enabled analyses of intron distribution and mobile-element dynamics, supporting epigenetic studies. The organism is also used in education as an accessible model for introductory molecular genetics.

Group I intron

Group I introns are self-splicing introns distributed throughout chloroplast, mitochondrial, and nuclear genomes. The reaction proceeds through a two-step transfer that uses an external guanosine nucleophile; an internal guide sequence and paired helices form the active site. The tertiary fold is stabilized by interactions between the P4/P6 and P3/P9 domains, with junction J8/7 as a landmark. Some Group I introns mobilize after excision via embedded homing endonuclease genes, affecting gene mobility. Evolutionarily, they are regarded as important agents in the origin of intron-exon architecture and genome innovation.