The RNA-centred view of the synapse: non-coding RNAs and synaptic plasticity

摘要

IfmRNAswere the onlyRNAsmade by a neuron, therewould be a simplemapping ofmRNAs to proteins.However,microRNAs and other non-codingRNAs (ncRNAs; endo-siRNAs, piRNAs, BC1, BC200, antisense and long ncRNAs, repeat-related transcripts, etc.) regulatemRNAs via effects on protein translation aswell as transcriptional and epigenetic mechanisms. Not only are genesONor OFF, but their ability to be translated can be turned ON or OFF at the level of synapses, supporting an enormous increase in information capacity. Here, I review evidence that ncRNAs are expressed pervasively within dendrites in mammalian brain; that some are activity-dependent and highly enriched near synapses; and that synaptic ncRNAs participate in plasticity responses including learning and memory. Ultimately, ncRNAs can be viewed as the post-it notes of the neuron. They have no literal meaning of their own, but derive their functions from where (and to what) they are stuck. This may explain, in part, why ncRNAs differ so dramatically from protein-coding genes, both in terms of the usual indicators of functionality and in terms of evolutionary constraints. ncRNAs do not appear to be direct mediators of synaptic transmission in the manner of neurotransmitters or receptors, yet they orchestrate synaptic plasticity-and may drive species-specific changes in cognition.