Long non-coding RNAs in nervous system function and disease

Irfan A. Qureshi, John S. Mattick, Mark F. Mehler

Research output: Contribution to journalArticle

300 Citations (Scopus)

Abstract

Central nervous system (CNS) development, homeostasis, stress responses, and plasticity are all mediated by epigenetic mechanisms that modulate gene expression and promote selective deployment of functional gene networks in response to complex profiles of interoceptive and environmental signals. Thus, not surprisingly, disruptions of these epigenetic processes are implicated in the pathogenesis of a spectrum of neurological and psychiatric diseases. Epigenetic mechanisms involve chromatin remodeling by relatively generic complexes that catalyze DNA methylation and various types of histone modifications. There is increasing evidence that these complexes are directed to their sites of action by long non-protein-coding RNAs (lncRNAs), of which there are tens if not hundreds of thousands specified in the genome. LncRNAs are transcribed in complex intergenic, overlapping and antisense patterns relative to adjacent protein-coding genes, suggesting that many lncRNAs regulate the expression of these genes. LncRNAs also participate in a wide array of subcellular processes, including the formation and function of cellular organelles. Most lncRNAs are transcribed in a developmentally regulated and cell type specific manner, particularly in the CNS, wherein over half of all lncRNAs are expressed. While the numerous biological functions of lncRNAs are yet to be characterized fully, a number of recent studies suggest that lnRNAs are important for mediating cell identity. This function seems to be especially important for generating the enormous array of regional neuronal and glial cell subtypes that are present in the CNS. Further studies have also begun to elucidate additional roles played by lncRNAs in CNS processes, including homeostasis, stress responses and plasticity. Herein, we review emerging evidence that highlights the expression and function of lncRNAs in the CNS and suggests that lncRNA deregulation is an important factor in various CNS pathologies including neurodevelopmental, neurodegenerative and neuroimmunological disorders, primary brain tumors, and psychiatric diseases.

Original languageEnglish (US)
Pages (from-to)20-35
Number of pages16
JournalBrain Research
Volume1338
DOIs
StatePublished - Jun 18 2010

Fingerprint

Long Noncoding RNA
Nervous System Diseases
Central Nervous System
Epigenomics
Psychiatry
Homeostasis
Histone Code
Genetic Epigenesis
Gene Expression
Chromatin Assembly and Disassembly
Gene Regulatory Networks
DNA Methylation
Brain Neoplasms
Neuroglia
Neurodegenerative Diseases
Organelles
Genome
Pathology

Keywords

  • CoREST
  • Epigenetic
  • Long non-coding RNA (lncRNA)
  • Neural stem cell (NSC)
  • Neuron
  • Non-coding RNA (ncRNA)
  • Oligodendrocyte
  • Repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Long non-coding RNAs in nervous system function and disease. / Qureshi, Irfan A.; Mattick, John S.; Mehler, Mark F.

In: Brain Research, Vol. 1338, 18.06.2010, p. 20-35.

Research output: Contribution to journalArticle

Qureshi, Irfan A. ; Mattick, John S. ; Mehler, Mark F. / Long non-coding RNAs in nervous system function and disease. In: Brain Research. 2010 ; Vol. 1338. pp. 20-35.
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