Cells (May 2021)

Codon Bias Can Determine Sorting of a Potassium Channel Protein

  • Anja J. Engel,
  • Marina Kithil,
  • Markus Langhans,
  • Oliver Rauh,
  • Matea Cartolano,
  • James L. Van Etten,
  • Anna Moroni,
  • Gerhard Thiel

Journal volume & issue
Vol. 10, no. 1128
p. 1128


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Due to the redundancy of the genetic code most amino acids are encoded by multiple synonymous codons. It has been proposed that a biased frequency of synonymous codons can affect the function of proteins by modulating distinct steps in transcription, translation and folding. Here, we use two similar prototype K+ channels as model systems to examine whether codon choice has an impact on protein sorting. By monitoring transient expression of GFP-tagged channels in mammalian cells, we find that one of the two channels is sorted in a codon and cell cycle-dependent manner either to mitochondria or the secretory pathway. The data establish that a gene with either rare or frequent codons serves, together with a cell-state-dependent decoding mechanism, as a secondary code for sorting intracellular membrane proteins.