Catalysis by RNA, Structural Themes: Group I Introns

Abstract

Many eukaryotic genes are interrupted by segments of DNA called intervening sequences or introns. These introns are transcribed into ribonucleic acid (RNA) along with the coding segments of gene, called exons. In most cases, the introns are removed from the RNA by a cellular apparatus called the spliceosome. In the presence of biologically relevant concentrations of magnesium and guanosine nucleoside, some introns, called group I introns, are capable of self-splicing: excising themselves from the flanking RNA, and religating the RNA exons to form a functional RNA. Group I introns are the relics of selfish genetic elements that carried with them genes encoding enzymes capable of integrating the entire genetic element into cellular DNA. The self-splicing activity of the RNA transcript allowed the element to have minimal impact upon the host gene. Group I introns are found within a diverse variety of genes including those encoding the energy-transducing machinery in mitochondria, ribosomal RNAs, transfer RNAs, and phage genes. By appropriate engineering, a group I intron can be converted into a multiple turnover RNA enzyme, or ribozyme, capable of cleaving single-stranded RNA substrates. The catalytic activity of these molecules depends on accurate folding into a three-dimensional structure that precisely positions both functional groups on the RNA and divalent metal ions to catalyze a specific phosphotransesterification reaction.