View Program - 63rd Annual Drosophila Research Conference

Codon bias occurs when certain codons appear more frequently in the coding genome than their synonymous counterparts. This phenomenon occurs throughout all forms of life and is important in determining protein expression at the steps of both transcription and translation. Although the impact of codon bias is only beginning to be studied during animal development and in different tissues, an understanding of how individual cell types respond to codon biased transcripts is beginning to emerge. We have undertaken one of the first studies to reveal cell and tissue-specific differences in codon bias in the model organism Drosophila and have uncovered some of the first evidence that tissues in the same animal respond differently to codon usage in vivo. Specifically, in cell types within the developing Drosophila brain, we find robust protein expression from reporters enriched in rarely used codons, whereas most other tissues in the fly do not express such reporters. Within the brain itself, neural stem cells are unable to express proteins encoded by rare-codon enriched genes, while differentiated neurons can. Cell identity appears tied to the ability to express transcripts enriched in rare codons, as experimentally blocking neuronal differentiation drastically reduces brain expression of a rare-codon enriched reporter. To uncover molecular regulators that enable neurons to specifically express rare-codon enriched reporters, we have initiated a reverse genetic screen. This screen used RNAi and the UAS-GAL4 system to knock down potential regulators enriched in neuroblasts or neurons. We assessed the role of each gene in enabling translation of rare-codon enriched transcripts by measuring expression of our rare-codon enriched reporter in neurons. Results of the screen will be presented at the poster. Using our Drosophila model, we may ultimately identify a new regulatory mechanism during neuronal development and function: cellular response to codon bias.

Response to and regulation of codon bias in Drosophila neural lineages.

**Response to and regulation of codon bias in Drosophila neural lineages.**