RNA in brain disease: No longer just the messenger in the middle

RNA research has made great progress in recent years. A variety of unforeseen complexities have been identified, many with relevance to human brain disease. For example, neurologic illnesses may arise because of perturbations in distinct but interrelated tiers of RNA-based genetic regulation: pre-mRNA splicing; nonsplicing RNA modifications; and mRNA translational regulation. Furthermore, there is poor correlation between mRNA levels and protein levels in mammalian cells, due partly to complicated post-transcriptional regulation by hitherto unknown noncoding RNAs. Some noncoding RNAs have been shown to be involved in human brain diseases. Diseases potentially mediated by alterations in RNA processes include tauopathies, myotonic dystrophy, Alzheimer disease, brain cancer, and many others. Here we present an overview of new research highlighting functions for RNA that far surpass the messenger in the middle role and that identify RNA molecules as important agents in the human brain in health and in disease states.