Virology, Nebraska Center for
Date of this Version
Engel, A.J.; Kithil, M.; Langhans, M.; Rauh, O.; Cartolano, M.; Van Etten, J.L.; Moroni, A.; Thiel, G. Codon Bias Can Determine Sorting of a Potassium Channel Protein. Cells 2021, 10, 1128. https://doi.org/ 10.3390/cells10051128
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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