Widespread differential expression of coding region and UTR sequences in neurons and other tissues

Mature messenger RNAs (mRNAs) consist of coding sequence (CDS) and 5’ and 3’ untranslated regions, 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, observing many genes with high UTR relative to CDS, and others with high CDS to UTR. By in situ hybridization 19 of 19 genes examined show a broad range of UTR to CDS expression ratios in different neurons and other tissues. These ratios may be spatially graded or change with developmental age, but are consistent across animals. Further, for two genes examined, a 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 UTR sequences in regulation of protein expression, and highlight the importance of separately examining UTR and CDS sequences in gene expression analyses. Overall design: dopamine or serotonin neuronal mRNA was purified selectively by using dopamine transporter (DAT) and SLC6A4 (serotonin transporter) BacTrap mice. RNA sequencing was carried out using Illumina HiSeq 2500.

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Kocabas A, Duarte T, Kumar S, Hynes MA