The emerging roles of long non-coding RNAs in the nervous system.

Tens, if not hundreds, of thousands of long non-coding RNAs (lncRNAs) are transcribed from mammalian genomes, especially in the brain, wherein most exhibit region-specific and/or cell-specific expression patterns. Many lncRNAs are nuclear-localized and appear to be the products of developmental enhancers, whereas others are found in the cytoplasm, including at the synapse. Here, we describe the lncRNAs that have been shown to have roles in various aspects of brain development, synaptic function, learning, behaviour and brain disorders. Our emerging understanding indicates that lncRNAs direct many, if not most, of the regulatory transactions that give rise to the structure of the brain and modulate its functions, probably through their guidance of relatively generic effector proteins. Although they hold promise as targets for therapeutic interventions, a concerted effort will be required to characterize the structures, functions, spatial distribution and interacting partners of the lncRNAs expressed in the brain, most of which have not been studied. We suggest that the lncRNAs transcribed from genomic regions associated with human neurological traits and disorders be prioritized for analysis.