Messenger RNA for glutamine synthetase. Review article.

Abstract

Of the various eucaryotic tissues, where glutamine synthetase (GS) mRNA and its regulation have been investigated, the induction of GS by glucocorticoids in the embryonic chick retina represents one of the systems most extensively studied. GS mRNA was first identified at the polysomal level by immunochemical precipitation of fractionated polysomes containing nascent GS chains with anti-GS gamma-globulin. The mRNA has been shown to be polyadenylated at the 3' end; on this basis, it has been partially purified from embryonic chick retina as well as from N. Crassa by chromatography on oligo(dT)-cellulose or poly(U)-sepharose and translated in cell-free protein synthesizing systems derived from wheat germ. Hormonal regulation of GS activity studied in the embryonic retina, hepatoma tissue culture cells, or in other tissues is always shown to be mediated by GS mRNA. In the retina, hydrocortisone (HC) elicits an age-related and transcription-dependent induction of GS by enhancing the level of GS mRNA in the polysomes through an increased supply of this mRNA from the nucleus. Comparative studies of three inhibitors of transcription, viz. actinomycin D, leucanthone and proflavine on the induction of GS by HC indicate that the latter inhibits GS mRNA selectively and reversibly with minimal effects on other RNA synthesis. Since proflavine acts by competing with HC-receptor binding sites in the nuclei, further studies on its interaction with the retina genome are likely to help identify the DNA sequences involved in the GS induction. In bacteria, studies on the genetics and physiology of various mutants with lesions in the structural gene for GS show that the transcription of the GS gene (gln A) is regulated both positively and negatively by GS and the product of another gene gln F. Purification of GS mRNA to homogeneity cloning of its cDNA and development of assay systems for cell-free transcription of GS are other studies likely to advance our knowledge on GS mRNA and its regulation.