Glutamine synthetase expression in perinatal spiny mouse liver

The pronounced increase in the protein/mRNA ratio of ammonia-metabolising e nzymes in fat liver in the last prenatal week represents a clear example of a post-transcriptional level of control of gene expression. Both the under lying mechanism, namely an increase in translational efficiency of the mRNA and/or enhanced stability of the protein, and its importance for perinatal adaptation are unknown. We investigated this process in spiny mouse liver, because the comparison of rat and spiny mouse can discriminate adaptively from developmentally regulated processes in the perinatal period. We focuse d on glutamine synthetase (GS) because of the conveniently small size of it s mRNA. Prenatally, GS enzyme activity slowly accumulated to approximate to 1.3 U . g(-1) liver at birth and postnatally more rapidly to 5.5 U . g(-1) at 2 weeks. Both phases of enzyme accumulation obeyed exponential function s. Western-blot analysis showed that changes in GS activity reflected chang es in GS protein content. GS mRNA content of the liver was 45 fmol . g(-1) at 2 weeks before birth and slowly declined to approximate to 25 fmol . g(- 1) at 2 weeks after birth. The GS protein/mRNA ratio increased 2.5-fold pre natally and sixfold postnatally. Analysis of prenatal and postnatal polysom e profiles revealed no evidence of GS mRNA-containing ribonucleoprotein par ticles. instead, GS mRNAs were (fully) occupied by 12 ribosomes, indicating regulation at the level of elongation. The kinetics of GS protein accumula tion, in conjunction with GS mRNA content, are consistent with an approxima te to sixfold increase in its rate of synthesis at birth as the result of a corresponding stimulation of the rate of elongation.