biostudies-literaturePeterson JNational Cancer InstituteNCI NIH HHS22166https://www.ebi.ac.uk/biostudies/studies/S-EPMC7746698biostudies-literatureUnknown10(1)The ability to translate three nucleotide sequences, or codons, into amino acids to form proteins is conserved across all organisms. All but two amino acids have multiple codons, and the frequency that such synonymous codons occur in genomes ranges from rare to common. Transcripts enriched in rare codons are typically associated with poor translation, but in certain settings can be robustly expressed, suggestive of codon-dependent regulation. Given this, we screened a gain-of-function library for human genes that increase the expression of a GFP^rare reporter encoded by rare codons. This screen identified multiple components of the mitogen activated protein kinase (MAPK) pathway enhancing GFP^rare expression. This effect was reversed with inhibitors of this pathway and Scientific reportsExpression of transgenes enriched in rare codons is enhanced by the MAPK pathway.PMC7746698R01 CA094184F32CA192715P01 CA203657T32 CA059365R01CA94184F32 CA192715Peterson JErdogan OLi SKaltenbrun ECounter CMfalseExpression of transgenes enriched in rare codons is enhanced by the MAPK pathway.The ability to translate three nucleotide sequences, or codons, into amino acids to form proteins is conserved across all organisms. All but two amino acids have multiple codons, and the frequency that such synonymous codons occur in genomes ranges from rare to common. Transcripts enriched in rare codons are typically associated with poor translation, but in certain settings can be robustly expressed, suggestive of codon-dependent regulation. Given this, we screened a gain-of-function library for human genes that increase the expression of a GFP^rare reporter encoded by rare codons. This screen identified multiple components of the mitogen activated protein kinase (MAPK) pathway enhancing GFP^rare expression. This effect was reversed with inhibitors of this pathway and 2020-01-01T00:00:00Z2020 Dec2026-05-07T12:52:25.475Z2025-06-01T00:20:25.46ZS-EPMC77466983333512710.1038/s41598-020-78453-5