Nature 477, 490–494 (2011)

Polyamines such as spermine are polycationic molecules with multiple cellular functions. In eukaryotes, polyamine biosynthesis involves the conversion of ornithine to putrescine by ornithine decarboxylase (ODC). The biosynthetic pathway is regulated by modulation of ODC concentrations in a peculiar process in which an ODC 'antizyme' (OAZ) disrupts ODC dimerization, thereby targeting it for degradation. Production of full-length OAZ1 protein in Saccharomyces cerevisiae requires +1 ribosomal frameshifting (RFS) during translation, a process that is enhanced by elevated polyamine concentrations. Kurian et al. now show that polyamines directly regulate antizyme expression by binding to the nascent OAZ1 polypeptide while it is still on the ribosome. A detailed analysis of OAZ1 mRNA revealed that sequences 5′ and 3′ to the RFS site were required to negatively regulate OAZ1 expression, but surprisingly, the regulatory element resides in the emerging OAZ1 polypeptide and not in the coding mRNA. An N-terminal polypeptide domain of OAZ1 negatively controls RFS whereas a C-terminal domain prevents completion of OAZ1 translation under low-polyamine conditions. Biochemical data showing direct polyamine binding to OAZ1 led the authors to a regulatory model explaining how elevated concentrations of polyamines enhance OAZ1 translation, leading to ODC turnover and downregulation of polyamine biosynthesis. This example of metabolite sensing by nascent polypeptides during translation may represent a new pathway for the regulation of gene expression in cells.