Abstract
We are attempting to delineate the molecular basis for both metabolite regulation of AS and enzyme overproduction in canavanine resistant (Canr) cells. We isolated normal and Canr variant lymphoblast cell lines from the parent of a citrullinemia patient. These cells contain one normal gene and one mutant allele producing an abnormal mRNA which is distinguishable by S1 nuclease analysis. Activities for AS (nmol/min/mg protein) were as follows: lymphoblasts in arginine medium <0.01; lymphoblasts in citrulline medium 0.05; three Canr lymphoblast variants 0.79-1.2. S1 nuclease analysis demonstrated parallel increases in both normal and abnormal RNA in the Canr cells in proportion to the increase in enzyme activity. Since selective pressure in the Canr isolation is restricted to the functional allele, the increased expression of the mutant allele must reflect a trans-acting mechanism affecting the expression of both alleles. We also have detected alternative RNA splicing involving the presence or absence of an exon (probably the 2nd exon) in the 5′ untranslated region of the mRNA. This exon is present in only a very minor proportion of mRNA from human liver or fibroblasts, but is present in a larger proportion of mRNA from Canr cells or baboon liver. The functional significance of this result is unclear at present.
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Beaudet, A., Freytag, S., Su, TS. et al. TRANS-ACTING REGULATION AND ALTERNATIVE RNA SPLICING FOR THE ARGININOSUCCINATE SYNTHETASE (AS) LOCUS. Pediatr Res 18 (Suppl 4), 219 (1984). https://doi.org/10.1203/00006450-198404001-00758
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DOI: https://doi.org/10.1203/00006450-198404001-00758