Nucleic Acids Research

Identification of novel post-transcriptional features in olfactory receptor family mRNAs

Shum, E. Y., Espinoza, J. L., Ramaiah, M., Wilkinson, M. F..

Olfactory receptor (Olfr) genes comprise the largest gene family in mice. Despite their importance in olfaction, most Olfr mRNAs remain uncharacterized. Using RNA-seq analysis, we annotated the repertoire of significantly expressed mouse Olfr mRNAs and found that they have several atypical features, suggesting that post-transcriptional regulation impacts their expression. First, many Olfr mRNAs are intronless and those with introns typically have a single intron at the 5' end. Second, Olfr mRNAs, as a group, have dramatically higher average AU content and lower predicted secondary structure than do control mRNAs. Third, Olfr mRNAs have a higher density of upstream open reading frames (uORFs) in their 5' UTR and AU-rich elements (AREs) in their 3' UTR than do control mRNAs. Fourth, Olfr mRNAs have much shorter 3' UTR regions and fewer predicted binding sites for microRNAs (miRNAs) that are expressed in the olfactory epithelium than do control mRNAs. All of these novel properties correlated with higher Olfr expression. We also identified striking differences in the ‘post-transcriptional features’ of the mRNAs from the two major classes of Olfr genes, a finding consistent with their independent evolutionary origin. Together, our results suggest that the Olfr gene family has encountered unusual selective forces in neural cells that have driven them to acquire unique post-transcriptional regulatory features. In support of this possibility, we found that while Olfr mRNAs are degraded by a deadenylation-dependent mechanism, they are largely protected from this decay in neural lineage cells.