Cells alter their behavior in response to physiological needs or when they detect exogenous small molecules (such as essential nutrients or deleterious toxins) through a broad range of mechanisms, including those of transmembrane receptors or feedback inhibition of enzymes in metabolic pathways. Polyamines are small organic compounds that possess multiple positive charges at physiological pH levels and help regulate cellular proliferation and differentiation. The first step in polyamine biosynthesis involves ornithine decarboxylase (ODC), an enzyme that converts ornithine to putrescine. ODC is regulated by the ODC antizyme, a small protein that targets ODC for ubiquitin-independent degradation by the proteasome. High intracellular concentrations of polyamines lead to an increase in the production of the ODC antizyme, which inhibits the activity of ODC and, thus, polyamine biosynthesis. Dohmen and colleagues now report how polyamines regulate the translation of the mRNA for OAZ1, the sole ODC antizyme in Saccharomyces cerevisiae. Translation of the full-length OAZ1 mRNA only occurs if a ribosomal frameshift event takes place in the middle of the transcript. The authors found that changes to the 5′ portion of the OAZ1 mRNA altered the efficiency of ribosomal frameshifting, but only the 3′ region of the transcript 'sensed' the presence of polyamines. Silent mutations in the OAZ1 mRNA 3′ portion did not alter polyamine-sensing, but mutations that changed residues very close to C-terminus of the OAZ1 polypeptide did. These observations revealed that polyamines directly bind to the nascent polypeptide while still associated with the ribosome–mRNA complex. The authors propose that when polyamine concentrations are low, depending on translational pausing caused by the frameshifting site, the nascent OAZ1 polypeptide assumes a conformation that leads to translational arrest; higher polyamine concentrations somehow prevent formation of this inhibitory conformation, allowing translation of full-length ODC antizyme to transpire. The exact mechanism by which this occurs is not yet clear, nor is it clear whether this unusual mRNA translational mechanism is unique to polyamines or whether other metabolites use this process to regulate enzymes in their own biosynthetic pathways. (Nature doi:10.1038/nature10393, published online 7 September 2011)