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

Autor: Stewart, Rebeccah K., Nguyen, Patrick, Laederach, Alain, Volkan, Pelin C., Sawyer, Jessica K., Fox, Donald T.
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Zdroj: Nature Communications; 6/20/2024, Vol. 15 Issue 1, p1-17, 17p
Abstrakt: 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. Messenger RNAs (mRNAs) harboring rare codons are upregulated in the Drosophila brain. In this study, the authors demonstrate that such rare codon mRNAs are present in Drosophila neurons but not in neuroblast cells, and that Orb2 positively regulates rare-codon-dependent mRNA stability in neurons. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index