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  • Regulation of non-coding RNA networks in the nervous system--what s the REST of the story?
  • Qureshi IA; Mehler MF
  • Neurosci Lett 2009[Dec]; 466 (2): 73-80
  • 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.
  • |Animals[MESH]
  • |Humans[MESH]
  • |Nervous System Diseases/etiology/genetics/metabolism[MESH]
  • |Nervous System/*metabolism[MESH]
  • |RNA, Untranslated/*metabolism[MESH]
  • |Repressor Proteins/genetics/metabolism/*physiology[MESH]

  • *{{pmid19679163}}
    *<b>[ Regulation of non-coding RNA networks in the nervous system--what s the REST of the story?]</b> Neurosci Lett 2009; 466(2) ; 73-80 Qureshi IA; Mehler MF


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    Neurosci Lett

    73 2.466 2009