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

Author:

Stewart Rebeccah K.,Nguyen PatrickORCID,Laederach AlainORCID,Volkan Pelin C.ORCID,Sawyer Jessica K.,Fox Donald T.ORCID

Abstract

AbstractRegulation 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.

Funder

American Cancer Society

U.S. Department of Health & Human Services | National Institutes of Health

Publisher

Springer Science and Business Media LLC

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