RNA expression at human fragile X synapses

The most prevalent genetic form of mental retardation, fragile X syndrome, is a single-gene disorder leading to loss of the RNA-binding protein FMRP. Loss of FMRP results in improper messenger RNA (mRNA) translation at synapses — the junctions between nerve cells — synaptic dysfunction, impaired cognitive function and autism-associated behaviors. To investigate the role of synaptic mRNA translation in normal synapse development, mRNAs and their functions need to be identified. While studies have examined the mRNA populations localized to synapses in rodent model systems, the identity of mRNAs at human synapses is unknown.

Neurotransmitters are released from a specialized region at the synapse. These regions are formed along axons, long projections that transmit information to other neurons or cells. Anne Marion Taylor and her colleagues at the University of North Carolina at Chapel Hill conducted the first study to identify the mRNA population targeted to axons of human glutamatergic neurons, one of the neuron types affected in fragile X. Emerging evidence suggests that translation within the axon may regulate proper synapse development.

The researchers used microfluidic technology developed previously by Taylor to obtain unique biochemical access to axons. They used gene expression microarrays to identify hundreds of mRNAs preferentially targeted to this compartment. They found that axons are enriched in transcripts involved in synaptic vesicle release, a process critical for synaptic transmission.