S

40S ribosomal 60S ribosomal subunit subunit

Self-Splicing Group I Introns Were the First Examples of Catalytic RNA

The DNA in the protozoan Tetrahymena thermophila contains an intervening intron in the region that encodes the large pre-rRNA molecule. Careful searches failed to uncover even one pre-rRNA gene without the extra sequence, indicating that splicing is required to produce mature rRNA in these organisms. In vitro studies showing that the pre-rRNA was spliced at the correct sites in the absence of any protein provided the first indication that RNA can function as a catalyst, like enzymes.

A whole raft of self-splicing sequences subsequently were found in pre-rRNAs from other single-celled organisms, in mitochondrial and chloroplast pre-rRNAs, in several pre-mRNAs from certain E. coli bacteriophages, and in some bacterial tRNA primary transcripts. The self-splicing sequences in all these precursors, referred to as group I introns, use guanosine as a cofactor and can fold by internal base pairing to juxtapose closely the two exons that must be joined. As discussed earlier, certain mitochondrial and chloroplast pre-mRNAs and tRNAs contain a second type of self-splicing intron, designated group II.

The splicing mechanisms used by group I introns, group II introns, and spliceosomes are generally similar, involving two transesterification reactions, which require no input of energy (Figure 12-35). Structural studies of the group I intron from Tetrahymena pre-rRNA combined with mutational and biochemical experiments have revealed that the RNA folds into a precise three-dimensional structure that, like protein enzymes, contains deep grooves for binding substrates and solvent-inaccessible regions that function in catalysis. The group I intron functions like a metalloenzyme to precisely orient the atoms that participate in the two transesterification reactions adjacent to catalytic Mg2+ ions. Considerable evidence now indicates that splicing by group II introns and by snRNAs in the spliceo-some also involves bound catalytic Mg2+ ions. In both the groups I and II self-splicing introns and probably in the spliceosome, RNA functions as a ribozyme, an RNA sequence with catalytic ability.

Self-splicing introns

Group I Group II

Spliceosome-catalyzed splicing of pre-mRNA

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