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

Mol Cell. 2021 Oct 7;81(19):3904-3918.e6. doi: 10.1016/j.molcel.2021.07.020. Epub 2021 Aug 9.

Abstract

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.

Keywords: HOL1; eIF5A; polyamine; spermidine; translation termination; translational control; transporter; uORF.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Biological Transport
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Eukaryotic Translation Initiation Factor 5A
  • Gene Expression Regulation, Fungal
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Open Reading Frames
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism
  • Polyamines / metabolism*
  • Protein Biosynthesis*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Cation Transport Proteins
  • Hol1 protein, S cerevisiae
  • Membrane Transport Proteins
  • Peptide Initiation Factors
  • Polyamines
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins