Methionine-Mediated Repression in Saccharomyces cerevisiae: a Pleiotropic Regulatory System Involving Methionyl Transfer Ribonucleic Acid and the Product of Gene eth2

Abstract

Detailed study of methionine-mediated repression of enzymes involved in methionine biosynthesis in Saccharomyces cerevisiae led to classification of these enzymes into two distinct regulatory groups. Group I comprises four enzymes specifically involved in different parts of methionine biosynthesis, namely, homoserine- O -transacetylase, homocysteine synthetase, adenosine triphosphate sulfurylase, and sulfite reductase. Repressibility of these enzymes is greatly decreased in strains carrying a genetically impaired methionyl-transfer ribonucleic acid (tRNA) synthetase (mutation ts − 296). Conditions leading to absence of repression in the mutant strain have been correlated with a sharp decrease in bulk tRNA met charging, whereas conditions which restore repressibility of group I enzymes also restore tRNA met charging. These findings implicate methionyl-tRNA in the regulatory process. However, the absence of a correlation in the wild type between methionyl-tRNA charging and the levels of methionine group I enzymes suggests that only a minor iso accepting species of tRNA met may be devoted with a regulatory function. Repressibility of the same four enzymes (group I) was also decreased in strains carrying the regulatory mutation eth2 r . Although structural genes coding for two of these enzymes, as well as mutations ts − 296 and eth2 r segregate independently to each other, synthesis of group I enzymes is coordinated. The pleiotropic regulatory system involved seems then to comprise beside a “regulatory methionyl tRNA met ,” another element, product of gene eth2 , which might correspond either to an aporepressor protein or to the “regulatory tRNA met ” itself. Regulation of group II enzymes is defined by response to exogenous methionine, absence of response to either mutations ts − 296 and eth2 r , and absence of coordinacy with group I enzymes. However, the two enzymes which belong to this group and are both involved in threonine and methionine biosynthesis undergo distinct regulatory patterns. One, aspartokinase, is subject to a bivalent repression exerted by threonine and methionine, and the other, homoserine dehydrogenase, is subject only to methionine-mediated repression. Participation of at least another aporepressor and another corepressor, different from the ones involved in regulation of group I enzymes, is discussed.