4.6 Article

Codon Bias Can Determine Sorting of a Potassium Channel Protein

Journal

CELLS
Volume 10, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/cells10051128

Keywords

codon usage; effect of synonymous codon exchange; membrane protein sorting; dual sorting

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Funding

  1. European Research Council (ERC) [495, 695078]
  2. DFG [SPP1926]
  3. Open Access Publishing Fund of Technical University of Darmstadt

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The study found that biased frequency of synonymous codons can affect protein localization within cells, thus modulating protein function through different steps such as transcription, translation, and folding.
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.

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