Recently we found that the nuclear localized small modulatory double-stranded (ds) RNA (smRNA) coding NRSE sequences triggered activation of transcription of NRSE genes in adult hippocampal neural stem cells. NRSE smRNA, which are non-coding dsRNAs about 20 bp in length, reside in the nucleus and play a critical role in mediating neuronal differentiation. These smRNAs carry the sequence of NRSE/RE1, which is recognized by the NRSF/REST transcription factor. The NRSE sequences are embedded widely in the genomic region, typically in promoters of neuron-specific genes. The mechanism of action appears to be mediated through a specific interaction between dsRNA and DNA/protein interaction, rather than through siRNA or miRNA. The discovery of smRNAs extends the important contribution of non-coding RNAs as key regulators of cell fate choice for adult neurogenesis.
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