Mutual regulation of noncoding RNAs and RNA modifications in psychopathology: Potential therapeutic targets for psychiatric disorders?

The human brain is specifically enriched for multiple classes of noncoding RNAs (ncRNAs) and for particular RNA modifications, both of which are increasingly recognized to contribute to the etiology and pathophysiology of psychiatric disorders. Here, we summarize the rapidly developing areas of basic research in brain-specific ncRNA biology and the functional and pathological consequences of different RNA modifications. In particular, multiple studies have identified mutual regulation between ncRNAs and RNA modifications. Specifically, RNA methylation of ncRNAs can regulate their cleavage and maturation, intracellular transport, stability, and ultimately their degradation. Alternatively, ncRNAs can affect RNA modifications by up- or down-regulating target protein expression or by altering their subcellular distribution, among several other effects. Growing clinical and preclinical research attention is currently being focused on exploring the pathological impacts and highly diverse molecular regulatory mechanisms of ncRNAs and RNA modifications in psychiatric disorders. Here, we review recent findings surrounding the mutual regulation between ncRNAs and RNA modifications in brain psychopathology. We also discuss advances in basic discovery and clinical translation or therapeutic potential of targeting ncRNAs and/or RNA modification regulators in psychiatric disorders.