TY - JOUR
T1 - Regulation of non-coding RNA networks in the nervous system-What's the REST of the story?
AU - Qureshi, Irfan A.
AU - Mehler, Mark F.
N1 - Funding Information:
M.F.M. is supported by grants from the National Institutes of Health ( NS38902 , MH66290 ), as well as by the Roslyn and Leslie Goldstein, the Mildred and Bernard H. Kayden, the Rosanne H. Silbermann and the Alpern Family Foundations.
PY - 2009/12/4
Y1 - 2009/12/4
N2 - Recent advances are now providing novel insights into the mechanisms that underlie how cellular complexity, diversity, and connectivity are encoded within the genome. The repressor element-1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) and non-coding RNAs (ncRNAs) are emerging as key regulators that seem to orchestrate almost every aspect of nervous system development, homeostasis, and plasticity. REST and its primary cofactor, CoREST, dynamically recruit highly malleable macromolecular complexes to widely distributed genomic regulatory sequences, including the repressor element-1/neuron restrictive silencer element (RE1/NRSE). Through epigenetic mechanisms, such as site-specific targeting and higher-order chromatin remodeling, REST and CoREST can mediate cell type- and developmental stage-specific gene repression, gene activation, and long-term gene silencing for protein-coding genes and for several classes of ncRNAs (e.g. microRNAs [miRNAs] and long ncRNAs). In turn, these ncRNAs have similarly been implicated in the regulation of chromatin architecture and dynamics, transcription, post-transcriptional processing, and RNA editing and trafficking. In addition, REST and CoREST expression and function are tightly regulated by context-specific transcriptional and post-transcriptional mechanisms including bidirectional feedback loops with various ncRNAs. Not surprisingly, deregulation of REST and ncRNAs are both implicated in the molecular pathophysiology underlying diverse disorders that range from brain cancer and stroke to neurodevelopmental and neurodegenerative diseases. This review summarizes emerging aspects of the complex mechanistic relationships between these intricately interlaced control systems for neural gene expression and function.
AB - Recent advances are now providing novel insights into the mechanisms that underlie how cellular complexity, diversity, and connectivity are encoded within the genome. The repressor element-1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) and non-coding RNAs (ncRNAs) are emerging as key regulators that seem to orchestrate almost every aspect of nervous system development, homeostasis, and plasticity. REST and its primary cofactor, CoREST, dynamically recruit highly malleable macromolecular complexes to widely distributed genomic regulatory sequences, including the repressor element-1/neuron restrictive silencer element (RE1/NRSE). Through epigenetic mechanisms, such as site-specific targeting and higher-order chromatin remodeling, REST and CoREST can mediate cell type- and developmental stage-specific gene repression, gene activation, and long-term gene silencing for protein-coding genes and for several classes of ncRNAs (e.g. microRNAs [miRNAs] and long ncRNAs). In turn, these ncRNAs have similarly been implicated in the regulation of chromatin architecture and dynamics, transcription, post-transcriptional processing, and RNA editing and trafficking. In addition, REST and CoREST expression and function are tightly regulated by context-specific transcriptional and post-transcriptional mechanisms including bidirectional feedback loops with various ncRNAs. Not surprisingly, deregulation of REST and ncRNAs are both implicated in the molecular pathophysiology underlying diverse disorders that range from brain cancer and stroke to neurodevelopmental and neurodegenerative diseases. This review summarizes emerging aspects of the complex mechanistic relationships between these intricately interlaced control systems for neural gene expression and function.
KW - CoREST
KW - Epigenetic
KW - Glia
KW - MicroRNA (miRNA)
KW - Neural stem cell
KW - Neuron
KW - Non-coding RNA (ncRNA)
KW - Oligodendrocyte
KW - Repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF)
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U2 - 10.1016/j.neulet.2009.07.093
DO - 10.1016/j.neulet.2009.07.093
M3 - Review article
C2 - 19679163
AN - SCOPUS:70350126990
SN - 0304-3940
VL - 466
SP - 73
EP - 80
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -