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Long range control circuits within mitochondria and between nucleus and mitochondria 2. genetic and biochemical analyses of suppressors which selectively alleviate the mitochondrial intron mutations



Long range control circuits within mitochondria and between nucleus and mitochondria 2. genetic and biochemical analyses of suppressors which selectively alleviate the mitochondrial intron mutations



Molecular and General Genetics 184(3): 493-503



Two dominant nuclear (NAM1-1 and NAM2-1) and 1 mitochondrial (mim2-1) suppressors [in Saccharomyces cerevisiae] were studied. The action spectrum of these suppressors on 433 mit- mutations located in various mitochondrial genes were analyzed; they preferentially alleviate the effects of mutations located within intron open reading frames of the cob-box gene. These suppressors permit the maturation of cytochrome b mRNA by restoring the synthesis of intron encoded protein(s) catalytically involved in splicing, i.e., mRNA-maturase(s) (cf. Lazowska et al. 1980). NAM1-1 is allele specific and gene non-specific: it suppresses mutations located within different introns. NAM2-1 and mim2-1 are intron-specific: they suppress mutations all located in the same (box7) intron of the cob-box gene. Analyses of cytochrome absorption spectra and mitochondrial translation products of cells in which the suppressors are associated with various other mit- mutations show that the suppressors restore cytochrome b and/or cytochrome oxidase (cox I) synthesis, as expected from their growth phenotype. This suppression is, however, only partial: some new polypeptides characteristic of the mit- mutations can be still detected in the presence of suppressor. Interestingly enough when box7 specific suppressors NAM2-1 and mim2-1 are associated with a complete cob-box deletion (leading to a total deficiency of cytochrome b and oxidase) partial restoration of cox I synthesis is observed while cytochrome b is still totally absent. In strains carrying NAM2-1 or mim2-1 the presence of cytochrome b gene is no longer required for the expression of the oxi3 gene pointing out to the possibility of mutational switch-on of silent genes, whether mitochondrial, mim2-1, or nuclear, NAM2-1. This switch-on would permit the synthesis of an active maturase acting as a substitute for the box7 maturase in order to splice the cytochrome b and oxidase mRNA.

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Accession: 005827361

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PMID: 7038398


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