Changes in translational yield regulate tissue-specific expression of beta-glucuronidase.

Abstract

The number of beta-glucuronidase (GUS; beta-D-glucuronoside glucuronosohydrolase, EC 3.2.1.31) molecules per cell varies as much as 12-fold among mouse tissues. To identify the regulatory mechanisms responsible, estimates of the rates of GUS protein synthesis (ks) and degradation (kd) were obtained for six tissues in the B6.PAC-Gusn mouse strain, which carries the N haplotype of the GUS gene. Differences in enzyme levels among tissues were predominantly due to differences in rates of enzyme synthesis; only brain differed significantly in the rate of protein degradation. Typically, tissues contain about 2 molecules of GUS mRNA per cell. Differences in GUS mRNA levels were found among tissues, but these were not sufficient to account for observed differences in ks. This suggests that tissues differ in translational yield, which is defined as the product of the efficiency with which the GUS message is translated and the fraction of newly made polypeptides that are successfully matured into GUS tetramers. Experimental estimates of translational yield confirmed that this is indeed a source of tissue differences in GUS gene regulation. This finding also proved to be true of the B haplotype of the GUS gene. The differential regulation of special-function genes is, in general, effected transcriptionally. In contrast, the differential regulation of several "housekeeping" genes has been reported to arise from changes in mRNA maturation and/or stability. It is now apparent that translational yield, which is an aspect of protein synthesis, can also serve as a differential regulatory mechanism.