We hope this resource inspires other neuroscientists to explore how synaptic mRNA localization and local protein synthesis contribute to the functional diversification of synapses. Many thanks to @erin-schuman.bsky.social, @marcvoo.bsky.social, @evakaulich.bsky.social, and all other co-authors!

Interestingly, genes enriched at both the protein and mRNA levels captured synapse diversity best, suggesting a key role for local protein synthesis in synapse diversification. Check out the preprint for more!

Although synaptic mRNAs represent only a fraction of the templates for the synaptic proteome - with many templates residing in the soma or in non-synaptic regions of dendrites and axons - the synaptic transcriptome reflects the synapse diversity captured by the proteome equally well.

Integrating transcriptome and proteome data, we identified ~90 genes with significantly correlated RNA-protein ratios across regions, involved in synaptic vesicle dynamics, receptor signaling, & calcium regulation, suggesting a key role for local protein synthesis in maintaining protein copy number.

How does this relate to local protein synthesis in neuronal processes?

Using transgenic mice to fluorescently label and then sort 13 synapse types in 5 brain regions, we identified ~4000 mRNAs enriched at synapses – some type-specific, others shared – and highlight region-specific enrichments of mRNAs encoding protein subunits or family members.

Chemical synapses across the brain are highly diverse and it is well established that this manifests at the molecular level. Previous work has primarily focused on the proteome, but here we extend this view and describe another layer of synapse diversity – synaptic transcriptome diversity.