Regulation of non-coding RNA networks in the nervous system-What's the REST of the story?

Irfan A. Qureshi, Mark F. Mehler

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)73-80
Number of pages8
JournalNeuroscience Letters
Volume466
Issue number2
DOIs
StatePublished - Dec 4 2009

Fingerprint

Untranslated RNA
Nervous System
Transcriptional Silencer Elements
Long Noncoding RNA
RNA Editing
Macromolecular Substances
Neurons
Chromatin Assembly and Disassembly
Gene Silencing
MicroRNAs
Epigenomics
Brain Neoplasms
Neurodegenerative Diseases
Transcriptional Activation
Genes
Chromatin
Homeostasis
Transcription Factors
Stroke
Genome

Keywords

  • CoREST
  • Epigenetic
  • Glia
  • MicroRNA (miRNA)
  • Neural stem cell
  • Neuron
  • Non-coding RNA (ncRNA)
  • Oligodendrocyte
  • Repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of non-coding RNA networks in the nervous system-What's the REST of the story? / Qureshi, Irfan A.; Mehler, Mark F.

In: Neuroscience Letters, Vol. 466, No. 2, 04.12.2009, p. 73-80.

Research output: Contribution to journalArticle

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