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Gene expression is influenced by codon usage bias. Nuclear mechanisms, including the CCR4-NOT complex and RNA exosome, regulate gene expression through transcriptional and mRNA stability effects, impacting human cells.

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Biology

Background:

  • Codon usage bias significantly impacts gene expression levels.
  • Previously, codon usage effects were primarily linked to translation-dependent processes.

Purpose of the Study:

  • To identify factors mediating codon usage effects on gene expression genome-wide.
  • To investigate the role of the CCR4-NOT complex and nuclear factors in codon usage-dependent gene expression.

Main Methods:

  • Unbiased genome-wide screening to identify relevant factors.
  • Analysis of the CCR4-NOT complex subunit CNOT4 and nuclear factors like the RNA exosome and PAXT complex.

Main Results:

  • CNOT4 influences codon usage-dependent gene expression via transcriptional effects on nuclear RNA levels.
  • Nuclear exosome and PAXT complex regulate nuclear mRNA stability through RNA quality control.
  • These mechanisms promote cytoplasmic accumulation of mRNAs with optimal codon usage.

Conclusions:

  • Nuclear mechanisms, distinct from co-translational decay, are crucial for codon usage-dependent gene expression in human cells.
  • Both transcriptional regulation by CNOT4 and mRNA stability control by nuclear exosome/PAXT complex are key players.