PLX041644

GSE123608: Codon usage optimization in pluripotent embryonic stem cells [tRNA sequencing]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The uneven use of synonymous codons in the transcriptome regulates the efficiency and fidelity of protein translation rates. Yet, the importance of this codon bias on regulating cell state-specific expression programs is currently debated. Here, we asked whether the gene expression program in the well-defined cell states of self-renewal and differentiation in embryonic stem cells is driven by optimized codon usage. Using ribosome and transcriptome profiling, we identified distinct codon signatures for human self-renewing and differentiating embryonic stem cells. One driver for the cell state-specific codon bias was the genomic GC-content of the differentially expressed genes and thus, determined by transcription rather than translation. However, by measuring the codon frequencies at the ribosomes active sites interacting with transfer RNAs (tRNA), we discovered that the wobble position tRNA modification inosine strongly influenced the codon optimization in self-renewing embryonic stem cells. This effect was conserved in mice and independent of the differentiationstimulus. In summary, we newly reveal how translational mechanisms based on RNAmodifications can shape optimized codon usage in embryonic stem cells. SOURCE: Sabine Dietmann Wellcome Trust/Medical Research Council Stem Cell Institute