Mex3a-dependent post-transcriptional silencing assures olfactory receptor diversity and axon guidance specificity [scRNA-Seq]

Singular olfactory receptor (OR) expression is critical for vertebrate olfaction because the sequence of the chosen OR protein determines both the receptive field and axon guidance properties of each olfactory sensory neuron (OSN). However, numerous single cell RNA-seq studies reveal that OSN progenitors co-transcribe seemingly random combinations of OR genes before a gradual transition to transcriptional singularity. Here, we show that MEX3A, a RING and KH domain protein expressed during polygenic OR transcription, prevents efficient OR protein expression before the emergence of a prevalent, transcriptionally dominant OR allele. Consequently, MEX3A deletion enhances OR mRNA and OR protein abundance in OSN progenitors, resulting in premature induction of Perk signaling, biased OR gene choice, and OSN axon mistargeting. Our experiments uncover a novel, post-transcriptional mechanism of OR gene regulation that assures that the identity of the expressed OR can influence the identity of the OSN only at the onset of singular OR choice. scRNA-Seq from whole or zonally microdissected olfactory epithelium from Mex3a cKO mice and WT littermate controls