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Stemness factor Mex3a times translation and protein trafficking to ensure robust differentiation of olfactory sensory neurons

ABSTRACT: During the switch from progenitor to differentiated cell, cellular physiology must change to accommodate increased translation and trafficking of membrane-bound proteins. We identify stemness factor Mex3a, expressed in immature olfactory sensory neurons (OSNs), as a key factor in ensuring proper neuronal differentiation by regulating mRNA translation and trafficking of cell surface proteins in the context of Unfolded Protein Response (UPR) signaling. Loss of Mex3a in immature OSNs leads to defects in cilia structure, cell surface protein expression, and planar cell polarity in mature OSNs. Proteomics reveal a Mex3a-dependent decrease in proteins related to vesicle transport, lipid metabolism, and ribosome biogenesis. We identify RNA and ubiquitin targets of Mex3a and provide evidence that Mex3a can confer K27 ubiquitin linkage on substrates. Finally, modulating cellular levels of Mex3a changes the recruitment of translation factors Serbp1 and p-eEF2 to ribosomes with possible effects on translation. Our data reveal how a stemness factor regulates development post-transcriptionally and post-translationally to ensure robust differentiation.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Marko Jovanovic Rachel Duffie

PROVIDER: MSV000100330 | MassIVE | Wed Dec 24 12:25:00 GMT 2025

REPOSITORIES: MassIVE

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Stemness factor Mex3a times translation and protein trafficking to ensure robust differentiation of olfactory sensory neurons

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