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

Abstract

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.

Roles of lncLingo2 and its derived miR‐876‐5p in the acquisition of opioid reinforcement

“…The investigation of neural and molecular pathways affecting the formation of associative memories attached to opioids holds promise for advancing treatment approaches aimed at preventing and reversing drug addiction. Increasing evidence indicates that modulation of ncRNAs performs an essential function in neurodevelopment, neurodegenerative diseases and mental diseases 32–35 . Moreover, recent studies discovered substantial modifications in the expression profiles of ncRNA owing to drug exposure and clarified the functions of several specific ncRNAs in drug addiction, 36–38 and the dysregulation of lncRNAs has been observed and characterized within the NAc of mice that were subjected to treatment with methamphetamine and cocaine, as well as in the midbrain of individuals with a history of cocaine usage 22,39 .…”

Aging Differentially Alters the Transcriptome and Landscape of Chromatin Accessibility in the Male and Female Mouse Hippocampus

“…5B). Gomafu expression has been shown to be regulated by estrogen in breast cancer cells 170 and by synaptic activity in neurons 86,87 , and although many alternatively spliced Gomafu isoforms have been identified, little is known about their distinct functions 86 . Therefore, the interplay of sex hormones and sex-biased expression and alternative splicing of regulatory factors may contribute to downstream sex-biased patterns in the hippocampus.…”

“…5B), many occurred in genes encoding nuclear proteins such as the polycomb repressive complex-2 protein EZH2, as well as other genes encoding DNA-binding proteins such as Hmga1, Rorc, Ccdc62 and Zmym5. Furthermore, we detected an A5SS event that showed sex-biased AS in Miat/Gomafu, an lncRNA that regulates splicing, represses transcription through association with the polycomb repressive complex and is implicated in anxiety and schizophrenia 86,87 . One of top ten most significant AS events in young hippocampus was an A3SS splicing event in Ift88, a transport protein important for primary cilia maintenance in neurons 88 .…”

“…5B). Gomafu expression has been shown to be regulated by estrogen in breast cancer cells 170 and by synaptic activity in neurons 86,87 , and although many alternatively spliced Gomafu isoforms have been identified, little is known about their distinct functions 86 .…”

Role of long non-coding RNA in chemoradiotherapy resistance of nasopharyngeal carcinoma

“…Long noncoding RNAs (LncRNAs) are transcripts exceeding 200 nucleotides that cannot encode proteins ( 7 ). They play a very important role in physiological and pathological regulation ( 8 ) ( Figure 1 ).…”