Translational autoregulation of the S. cerevisiae high-affinity polyamine transporter Hol1.

Polyamines, small organic polycations, are essential for cell viability, and their physiological levels are homeostatically maintained by post-transcriptional regulation of key biosynthetic enzymes. In addition to de novo synthesis, cells can also take up polyamines; however, identifying cellular polyamine transporters has been challenging. Here we show that the S. cerevisiae HOL1 mRNA is under translational control by polyamines, and we reveal that the encoded membrane transporter Hol1 is a high-affinity polyamine transporter and is required for yeast growth under limiting polyamine conditions. Moreover, we show that polyamine inhibition of the translation factor eIF5A impairs translation termination at a Pro-Ser-stop motif in a conserved upstream open reading frame on the HOL1 mRNA to repress Hol1 synthesis under conditions of elevated polyamines. Our findings reveal that polyamine transport, like polyamine biosynthesis, is under translational autoregulation by polyamines in yeast, highlighting the extensive control cells impose on polyamine levels. [Display omitted] • Hol1 is the major high-affinity polyamine transporter in S. cerevisiae • Polyamine levels autoregulate HOL1 mRNA translation through a conserved uORF • Polyamines inhibit eIF5A to impair translation termination on the uORF • Ribosome stalling on the uORF prevents HOL1 translation Vindu et al. identify Hol1 as the major high-affinity polyamine transporter in S. cerevisiae. Polyamines autoregulate HOL1 expression through feedback inhibition of HOL1 mRNA translation mediated by polyamine inhibition of eIF5A-dependent translation termination on a conserved upstream open reading frame in the HOL1 mRNA leader. [ABSTRACT FROM AUTHOR]