Abstract
BACKGROUND/OBJECTIVES: Neural differentiation requires a multifaceted program to alter gene expression along the proliferation to the differentiation axis. While critical changes occur at the level of transcription, post-transcriptional mechanisms allow fine-tuning of protein output. We investigated the role of tRNAs in regulating gene expression during neural differentiation in Drosophila larval brains. METHODS: We quantified tRNA abundance in neural progenitor-biased and neuron-biased brains using the hydrotRNA-seq method. These tRNA data were combined with cell type-specific mRNA decay measurements and transcriptome profiles in order to model how tRNA abundance affects mRNA stability and translation efficiency. RESULTS: We found that (1) tRNA abundance is largely constant between neural progenitors and neurons but significant variation exists for 10 nuclear tRNA genes and 8 corresponding anticodon groups, (2) tRNA abundance correlates with codon-mediated mRNA decay in neuroblasts and neurons, but does not completely explain the different stabilizing or destabilizing effects of certain codons, and (3) changes in tRNA levels support a shift in translation optimization from a program supporting proliferation to a program supporting differentiation. CONCLUSIONS: These findings reveal coordination between tRNA expression and codon usage in transcripts that regulate neural development.