Mutation of a highly conserved base in the yeast mitochondrial 21S rRNA restricts ribosomal frameshifting.

ABSTRACT

A mutation shown to cause resistance to chloramphenicol in Saccharomyces cerevisiae was mapped to the central loop in domain V of the yeast mitochondrial 21S rRNA. The mutant 21S rRNA has a base pair exchange from U2677 (corresponding to U2504 in Escherichia coli) to C2677, which significantly reduces rightward frameshifting at a UU UUU UCC A site in a +1 U mutant. There is evidence to suggest that this reduction also applies to leftward frameshifting at the same site in a -1 U mutant. The mutation did not increase the rate of misreading of a number of mitochondrial missense, nonsense or frameshift (of both signs) mutations, and did not adversely affect the synthesis of wild-type mitochondrial gene products. It is suggested here that ribosomes bearing either the C2677 mutation or its wild-type allele may behave identically during normal decoding and only differ at sites where a ribosomal stall, by permitting non-standard decoding, differentially affects the normal interaction of tRNAs with the chloramphenicol resistant domain V. Chloramphenicol-resistant mutations mapping at two other sites in domain V are described. These mutations had no effect on frameshifting.