The Long Non-Coding RNA GOMAFU in Schizophrenia: Function, Disease Risk, and Beyond

Neuropsychiatric diseases are among the most common brain developmental disorders, represented by schizophrenia (SZ). The complex multifactorial etiology of SZ remains poorly understood, which reflects genetic vulnerabilities and environmental risks that affect numerous genes and biological pathways. Besides the dysregulation of protein-coding genes, recent discoveries demonstrate that abnormalities associated with non-coding RNAs, including microRNAs and long non-coding RNAs (lncRNAs), also contribute to the pathogenesis of SZ. lncRNAs are an actively evolving family of non-coding RNAs that harbor greater than 200 nucleotides but do not encode for proteins. In general, lncRNA genes are poorly conserved. The large number of lncRNAs specifically expressed in the human brain, together with the genetic alterations and dysregulation of lncRNA genes in the SZ brain, suggests a critical role in normal cognitive function and the pathogenesis of neuropsychiatric diseases. A particular lncRNA of interest is GOMAFU, also known as MIAT and RNCR2. Growing evidence suggests the function of GOMAFU in governing neuronal development and its potential roles as a risk factor and biomarker for SZ, which will be reviewed in this article. Moreover, we discuss the potential mechanisms through which GOMAFU regulates molecular pathways, including its subcellular localization and interaction with RNA-binding proteins, and how interruption to GOMAFU pathways may contribute to the pathogenesis of SZ.