Integrating the roles of long and small non-coding RNA in brain function and disease

Regulatory RNA is emerging as the major architect of cognitive evolution and innovation in the mammalian brain. While the protein machinery has remained largely constant throughout animal evolution, the non protein-coding transcriptome has expanded considerably to provide essential and widespread cellular regulation, partly through directing generic protein function. Both long (long non-coding RNA) and small non-coding RNAs (for example, microRNA) have been demonstrated to be essential for brain development and higher cognitive abilities, and to be involved in psychiatric disease. Long non-coding RNAs, highly expressed in the brain and expanded in mammalian genomes, provide tissue- and activity-specific epigenetic and transcriptional regulation, partly through functional control of evolutionary conserved effector small RNA activity. However, increased cognitive sophistication has likely introduced concomitant psychiatric vulnerabilities, predisposing to conditions such as autism and schizophrenia, and cooperation between regulatory and effector RNAs may underlie neural complexity and concomitant fragility in the human brain.