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Orb2 enables rare-codon-enriched mRNA expression during Drosophila neuron differentiation

Author

Listed:
  • Rebeccah K. Stewart

    (Duke University
    Duke University)

  • Patrick Nguyen

    (Duke University)

  • Alain Laederach

    (University of North Carolina)

  • Pelin C. Volkan

    (Duke University)

  • Jessica K. Sawyer

    (Duke University
    Duke University)

  • Donald T. Fox

    (Duke University
    Duke University)

Abstract

Regulation of codon optimality is an increasingly appreciated layer of cell- and tissue-specific protein expression control. Here, we use codon-modified reporters to show that differentiation of Drosophila neural stem cells into neurons enables protein expression from rare-codon-enriched genes. From a candidate screen, we identify the cytoplasmic polyadenylation element binding (CPEB) protein Orb2 as a positive regulator of rare-codon-dependent mRNA stability in neurons. Using RNA sequencing, we reveal that Orb2-upregulated mRNAs in the brain with abundant Orb2 binding sites have a rare-codon bias. From these Orb2-regulated mRNAs, we demonstrate that rare-codon enrichment is important for mRNA stability and social behavior function of the metabotropic glutamate receptor (mGluR). Our findings reveal a molecular mechanism by which neural stem cell differentiation shifts genetic code regulation to enable critical mRNA stability and protein expression.

Suggested Citation

  • Rebeccah K. Stewart & Patrick Nguyen & Alain Laederach & Pelin C. Volkan & Jessica K. Sawyer & Donald T. Fox, 2024. "Orb2 enables rare-codon-enriched mRNA expression during Drosophila neuron differentiation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48344-8
    DOI: 10.1038/s41467-024-48344-8
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