Eukaryotic gene expression: Metabolite control by amino acids

Depletion of a single amino acid from the growth medium of most unicellular organisms leads to an increased transcription of genes coding for the enzymes in the cognate pathway. The consequences of amino-acid starvation are the reduction of both the intracellular pool and the corresponding charged transfer RNA. These effects, along with ribosome stalling, are the basis for transcription termination control in bacteria. Within the leader sequence are two tryptophan codons (UGG); when the cellular content of this amino acid is sufficient, the ribosome translates through these codons, triggering a messenger RNA secondary structure that acts as a termination signal for further transcription. Transcriptional initiation also is regulated in an amino acid-dependent manner through a tryptophan-activated repressor protein that specifically binds to the tryptophan operon promoter. In contrast to unicellular organisms, additional levels of control exist in mammals. In vivo, a change in metabolite concentration can cause corresponding changes in enzyme activity through complex hormonal or neural processes, rather than through direct transcriptional or translational control by substrate signaling. Most mammalian cells express the enzyme asparagine synthetase that is responsible for the biosynthesis of asparagine from aspartate and glutamine. The intimate relationship between amino-acid supply and the fundamental cellular process of protein synthesis makes the amino acid-dependent control of gene expression particularly important. © 1996 Academic Press Inc.