Glucocorticoids selectively inhibit translation of ribosomal protein mRNAs in P1798 lymphosarcoma cells.

When P1798 murine lymphosarcoma cells are exposed to 10(-7) M dexamethasone, there is a dramatic inhibition of rRNA synthesis, which is completely reversible when the hormone is withdrawn. In the present experiments we examined whether dexamethasone treatment causes any alteration in the accumulation or utilization of mRNAs that encode ribosomal proteins (rp mRNAs). No effect on the accumulation of six different rp mRNAs was detected. However, the translation of five of six rp mRNAs was selectively inhibited in the presence of the hormone, as judged by a substantial decrease in ribosomal loading. Normal translation of rp mRNA was resumed within a few hours after hormone withdrawal. In untreated or fully recovered cells, the distribution of rp mRNAs between polyribosomes and free ribonucleoprotein is distinctly bimodal, suggesting that rp mRNAs are subject to a particular form of translational control in which they are either translationally inactive or fully loaded with ribosomes. A possible relationship between this mode of translational control and the selective suppression of rp mRNA translation by glucocorticoids is discussed.     

Reduced Dosage of Genes Encoding Ribosomal Protein S18 Suppresses a Mitochondrial Initiation Codon Mutation in Saccharomyces Cerevisiae

A yeast mitochondrial translation initiation codon mutation affecting the gene for cytochrome oxidase subunit III (COX3) was partially suppressed by a spontaneous nuclear mutation. The suppressor mutation also caused cold-sensitive fermentative growth on glucose medium. Suppression and cold sensitivity resulted from inactivation of the gene product of RPS18A, one of two unlinked genes that code the essential cytoplasmic small subunit ribosomal protein termed S18 in yeast. The two S18 genes differ only by 21 silent substitutions in their exons; both are interrupted by a single intron after the 15th codon. Yeast S18 is homologous to the human S11 (70% identical) and the Escherichia coli S17 (35% identical) ribosomal proteins. This highly conserved family of ribosomal proteins has been implicated in maintenance of translational accuracy and is essential for assembly of the small ribosomal subunit. Characterization of the original rps18a-1 missense mutant and rps18aΔ and rps18bΔ null mutants revealed that levels of suppression, cold sensitivity and paromomycin sensitivity all varied directly with a limitation of small ribosomal subunits. The rps18a-1 mutant was most affected, followed by rps18aΔ then rps18bΔ. Mitochondrial mutations that decreased COX3 expression without altering the initiation codon were not suppressed. This allele specificity implicates mitochondrial translation in the mechanism of suppression. We could not detect an epitope-tagged variant of S18 in mitochondria. Thus, it appears that suppression of the mitochondrial translation initiation defect is caused indirectly by reduced levels of cytoplasmic small ribosomal subunits, leading to changes in either cytoplasmic translational accuracy or the relative levels of cytoplasmic translation products.