The long noncoding RNA RMST interacts with SOX2 to regulate neurogenesis.
Long 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.
Stem Cell and Developmental Biology Group, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
Shi-Yan
SY
Ng
Gireesh K
GK
Bogu
Boon Seng
BS
Soh
Lawrence W
LW
Stanton
D017398:Alternative Splicing; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells; D055495:Neurogenesis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C121019:RCOR1 protein, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors