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Codon usage optimization in pluripotent embryonic stem cells.

Susanne Bornelöv1, Tommaso Selmi2, Sophia Flad2,3

  • 1Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK.

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|June 9, 2019
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Summary
This summary is machine-generated.

Cell differentiation involves distinct codon usage patterns, influenced by GC content and tRNA modifications. Self-renewing embryonic stem cells prioritize codons optimized by inosine for efficient protein translation.

Keywords:
Codon biasDifferentiationStem cell self-renewaltRNA modifications

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Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Codon usage bias influences protein translation efficiency and fidelity.
  • The role of codon bias in cell state-specific gene expression is under investigation.
  • This study examines codon usage in embryonic stem cells during self-renewal and differentiation.

Purpose of the Study:

  • To investigate whether codon usage controls gene expression programs in self-renewing versus differentiating embryonic stem cells.
  • To identify distinct codon signatures associated with human embryonic stem cell differentiation.
  • To explore the relationship between guanine-cytosine (GC) content and cell state-specific codon bias.

Main Methods:

  • Ribosome profiling and transcriptome analysis were employed.
  • Codon frequencies at ribosome-tRNA interaction sites were measured.
  • Inosine levels in transfer RNAs (tRNAs) were assessed.

Main Results:

  • Distinct codon signatures were identified during human embryonic stem cell differentiation.
  • Cell state-specific codon bias is linked to the GC content of differentially expressed genes.
  • Self-renewing cells optimize translation of specific codons via inosine tRNA modification, with higher inosine levels observed in pluripotent stem cells.
  • This phenomenon is conserved in mice and stimulus-independent.

Conclusions:

  • GC content impacts cell state-specific mRNA levels.
  • Translational mechanisms involving tRNA modifications alter codon usage in embryonic stem cells.
  • Codon usage bias plays a role in regulating cell state-specific gene expression programs.