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

Abstract

If mRNAs were the only RNAs made by a neuron, there would be a simple mapping of mRNAs to proteins. However, microRNAs and other non-coding RNAs (ncRNAs; endo-siRNAs, piRNAs, BC1, BC200, antisense and long ncRNAs, repeat-related transcripts, etc.) regulate mRNAs via effects on protein translation as well as transcriptional and epigenetic mechanisms. Not only are genes ON or 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.

The role of epigenetic-related codes in neurocomputation: dynamic hardware in the brain

“…We do not see the process as modifying the software exactly: rather that the brain appears to be able, to some extent, to change its structural hardware, so as to process variations of software the better. This hardware particularly involves the modulation of the fine detail of the microanatomy of dendritic spines by epigenetic-related miRNAs, as presented elsewhere in this volume by Smalheiser [73]. We hope that computer scientists will develop more details of how this modulation could take place.…”

Non-coding mechanisms of local mRNA translation in neuronal dendrites

“…Recent advances in massive parallel RNA sequencing technologies have led to the identification of novel classes of small RNAs that are expressed in various tissues, including the mammalian brain (Smalheiser, 2014). PIWI (P-element induced wimpy testis)-interacting RNAs (piRNAs) are 25-35 nts long and typically arise from long, intergenic transcripts that are enriched in transposon and repeat elements (Aravin et al, 2007).…”

Rediscovering Don Swanson:The Past, Present and Future of Literature-based Discovery

“…It took us a decade to find provisional experimental evidence that this may, indeed, be the case (Smalheiser, 2012a, 2014). …”