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MiR-137 and GOMAFU form a novel non-coding RNA pathway to regulate human neuron differentiation and molecular networks affected in neuropsychiatric diseases

ABSTRACT: Increasing evidence suggests important roles of long noncoding RNAs (lncRNAs) in normal neuron development and neuropsychiatric disorders that disturb early neurodevelopmental processes. One such lncRNA is GOMAFU, which displays aberrant expression in schizophrenia postmortem brains and is known to regulate SCZ-associated splice variants in developing human neurons. However, molecular mechanisms that control expression and biological function of GOMAFU in human neuron development remain elusive. Here we report the identification of a novel miRNA-lncRNA pathway in which miR-137, a well-recognized risk factor for SCZ and autism spectrum disorder (ASD) that play key roles in promoting neuronal differentiation, enhances GOMAFU expression in human neurons through targeting transcription factors that suppress GOMAFU. In addition, loss of GOMAFU in cortical neurons derived from human induced pluripotent stem cells (hiPSCs) by CRISPR-cas9 mediated gene editing significantly reduces dendritic growth during early-stage differentiation. Moreover, GOMAFU deficiency elicited a broad influence on molecular pathways commonly affected in SCZ and ASD postmortem brains, including aberrantly increased expression of numerous genes known to govern neuroimmune responses. Our studies demonstrated essential roles of the lncRNA GOMAFU in human neuron development and connected GOMAFU malfunction with pathological molecular networks in neuropsychiatric disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182370 | GEO | 2023/10/03

REPOSITORIES: GEO

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