Metabolite-dependent regulation of gene expression in Trypanosoma brucei

Mechanisms regulating gene expression in trypanosomatid protozoa differ significantly from those in other eukaryotes. Transcription of the genome appears to be more or less constitutive with the polyadenylation and trans-splicing of large polycistronic RNAs producing monocistronic RNAs whose translation may then depend upon information within their 3' untranslated regions (3'UTRs). Various 3'UTR sequences involved in life-cycle stage-dependent differential gene expression have been described. Moreover, several RNA-binding proteins have been implicated in regulating expression of these transcripts through altering either their stability or their ability to interact with ribosomes. In this issue of Molecular Microbiology Xiao et al. report on a regulatory element within the 3'UTR of the transcript that encodes the polyamine pathway regulatory protein called prozyme. It appears that the RNA element controls translation of the prozyme RNA causing expression to be upregulated when levels of decarboxylated S-adenosylmethionine (dcAdoMet) are depleted. Since prozyme activates the enzyme S-adenosylmethionine decarboxylase (AdoMetDC), which is responsible for the production of dcAdoMet, losing this metabolite leads to upregulation of prozyme, activation of AdoMetDC and restoration of optimal levels of dcAdomet. The system thus represents a novel metabolite-sensing regulatory circuit that maintains polyamine homeostasis in these cells.