Widespread Differential Expression of Coding Region and 3′ UTR Sequences in Neurons and Other Tissues

• mRNA coding (CDS) and cognate 3′ UTR regions show widespread unbalanced expression
• A given gene can show a broad range of 3′ UTR to CDS expression ratios across neurons/cells
• Ratios are spatially graded and change with age but are consistent across embryos
• A high 3′ UTR-to-CDS ratio may predict lower protein level

SummaryMature messenger RNAs (mRNAs) consist of coding sequence (CDS) and 5′ and 3′ UTRs, typically expected to show similar abundance within a given neuron. Examining mRNA from defined neurons, we unexpectedly show extremely common unbalanced expression of cognate 3′ UTR and CDS sequences; many genes show high 3′ UTR relative to CDS, others show high CDS to 3′ UTR. In situ hybridization (19 of 19 genes) shows a broad range of 3′ UTR-to-CDS expression ratios across neurons and tissues. Ratios may be spatially graded or change with developmental age but are consistent across animals. Further, for two genes examined, a 3′ UTR-to-CDS ratio above a particular threshold in any given neuron correlated with reduced or undetectable protein expression. Our findings raise questions about the role of isolated 3′ UTR sequences in regulation of protein expression and highlight the importance of separately examining 3′ UTR and CDS sequences in gene expression analyses.