The Long Noncoding RNA RMST Interacts with SOX2 to Regulate Neurogenesis

• The lncRNA RMST is necessary for neuronal differentiation
• RMST is repressed by REST, a master transcription factor controlling key neuronal genes
• RMST associates with RNA-binding protein hnRNPA2/B1 and transcription factor SOX2
• RMST binds to promoters of SOX2 target genes and activates gene transcription

SummaryLong noncoding RNAs (lncRNAs) are abundant in the mammalian transcriptome, and many are specifically expressed in the brain. We have identified a group of lncRNAs, including rhabdomyosarcoma 2-associated transcript (RMST), which are indispensable for neurogenesis. Here, we provide mechanistic insight into the role of human RMST in modulating neurogenesis. RMST expression is specific to the brain, regulated by the transcriptional repressor REST, and increases during neuronal differentiation, indicating a role in neurogenesis. RMST physically interacts with SOX2, a transcription factor known to regulate neural fate. RMST and SOX2 coregulate a large pool of downstream genes implicated in neurogenesis. Through RNA interference and genome-wide SOX2 binding studies, we found that RMST is required for the binding of SOX2 to promoter regions of neurogenic transcription factors. These results establish the role of RMST as a transcriptional coregulator of SOX2 and a key player in the regulation of neural stem cell fate.

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