A small modulatory dsRNA specifies the fate of adult neural stem cells.
Discovering the molecular mechanisms that regulate neuron-specific gene expression remains a central challenge for CNS research. Here, we report that small, noncoding double-stranded (ds) RNAs play a critical role in mediating neuronal differentiation. The sequence defined by this dsRNA is NRSE/RE1, which is recognized by NRSF/REST, known primarily as a negative transcriptional regulator that restricts neuronal gene expression to neurons. The NRSE dsRNA can trigger gene expression of neuron-specific genes through interaction with NRSF/REST transcriptional machinery, resulting in the transition from neural stem cells with neuron-specific genes silenced by NRSF/REST into cells with neuronal identity that can express neuronal genes. The mechanism of action appears to be mediated through a dsRNA/protein interaction, rather than through siRNA or miRNA. The discovery of small modulatory dsRNAs (smRNAs) extends the important contribution of noncoding RNAs as key regulators of cell behavior at both transcriptional and posttranscriptional levels.
Kuwabara
Tomoko
T
Laboratory of Genetics, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hsieh
Jenny
J
Nakashima
Kinichi
K
Taira
Kazunari
K
Gage
Fred H
FH
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006801:Humans; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D012330:RNA, Double-Stranded / Q000235:genetics*; D012342:RNA, Small Nuclear / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D037941:Silencer Elements, Transcriptional / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D000099229:RE1-Silencing Transcription Factor
D012330:RNA, Double-Stranded; D012342:RNA, Small Nuclear; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor