TY - JOUR
T1 - A small modulatory dsRNA specifies the fate of adult neural stem cells
AU - Kuwabara, Tomoko
AU - Hsieh, Jenny
AU - Nakashima, Kinichi
AU - Taira, Kazunari
AU - Gage, Fred H.
N1 - Funding Information:
We thank David Anderson for the gift of the NRSF/REST antibodies and myc-tagged NRSF/REST constructs. We thank Andrew Fire and Tony Hunter for critical reviewing of our manuscript. We are grateful for the technical assistance of Lynne Moore and Bobbi Miller and to M.L. Gage for editorial comments. K.N. was supported by a JSPS Postdoctoral Fellowship for Research Abroad. J.H. was supported by the Hewitt Foundation for Medical Research. T.K. and K.T. were supported by various grants from AIST and Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan. F.H.G. was supported by the Lookout Fund, The Christopher Reeves Paralysis Foundation, Michael J. Fox Foundation, and the National Institutes of Health: National Institute on Aging, and National Institute of Neurological Disease and Stroke.
PY - 2004/3/19
Y1 - 2004/3/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1642603947&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1642603947&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(04)00248-X
DO - 10.1016/S0092-8674(04)00248-X
M3 - Article
C2 - 15035981
AN - SCOPUS:1642603947
SN - 0092-8674
VL - 116
SP - 779
EP - 793
JO - Cell
JF - Cell
IS - 6
ER -