The central role of noncoding RNA in the brain.

Less than 3% of the human genome generates protein-coding transcripts; the majority, far from being strewn with evolutionary "junk," is dynamically transcribed into non(protein)-coding RNAs (ncRNAs). These ncRNAs provide another provide another, previously hidden, level of regulatory information that appears to be involved in hard- and soft-wired epigentic processes. The extensive and intricate level of gene regulation provided by ncRNAs may be the major driver for the accelerated development of the human brain and its associated increase in complexity and cognition. Support for this is provided by the correlation between the evolutionary increase of complexity in the nonprotein-coding transcriptome paralleling cognitive evolution in primates, in contrast to the coincidently modest evolutionary changes of the protein-coding transcriptome. The essential role of these regulatory RNAs is reflected in almost every aspect in neuroscience, including chromatin modification, transcriptional regulation, alternative splicing, RNA editing and translation. Dissecting this plethora of regulatory networks and editing events, which are orchestrated through long and small noncoding RNAs, and their interaction with transcription factors, chromatin-modifying enzymes, and other protein effectors will provide essential insights into the transcriptional complexity and plasticity in the development and function of the human brain. Such complexity provides susceptibility to internal and external perturbations, which in rare cases might act as evolutionary catalysts, but in many cases could manifest as neuropsychiatric or neurodegenerative diseases. NcRNAs (especially lncRNAs) are therefore excellent candidates for both disease biomarkers and disease-ameliorating therapies.