Long non-coding RNAs in nervous system function and disease

Qureshi, Irfan A., Mattick, John S. and Mehler, Mark F. (2010) Long non-coding RNAs in nervous system function and disease. Brain Research, 1338 5: 20-35. doi:10.1016/j.brainres.2010.03.110


Author Qureshi, Irfan A.
Mattick, John S.
Mehler, Mark F.
Title Long non-coding RNAs in nervous system function and disease
Journal name Brain Research   Check publisher's open access policy
ISSN 0006-8993
1872-6240
Publication date 2010-06-18
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.brainres.2010.03.110
Open Access Status Not Open Access
Volume 1338
Issue 5
Start page 20
End page 35
Total pages 16
Editor Irwin B. Levitan
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Abstract Only relatively recently has it become clear that mammalian genomes encode tens of thousands of long non-coding RNAs (lncRNAs). A striking 40% of these are expressed specifically in the brain, where they show precisely regulated temporal and spatial expression patterns. This begs the question, what is the functional role of these many lncRNA transcripts in the brain? Here we canvass a growing number of mechanistic studies that have elucidated central roles for lncRNAs in the regulation of nervous system development and function. We also survey studies indicating that neurological and psychiatric disorders may ensue when these mechanisms break down. Finally, we synthesize these insights with evidence from comparative genomics to argue that lncRNAs may have played important roles in brain evolution, by virtue of their abundant sequence innovation in mammals and plausible mechanistic connections to the adaptive processes that occurred recently in the primate and human lineages.
Formatted 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.
© 2010 Elsevier B.V. All rights reserved.
Keyword 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)
Genome-wide association
Restless legs syndrome
Embryonic stem-cells
Oligodendrocyte lineage maturation
Cd8(+) T-cells
Messenger-RNA
Antisense RNA
Reelin gene
Huntingtons-disease
Alzheimers-disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Special issue: RNA mechanisms in CNS Systems and Disorders.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 11 Jul 2010, 10:08:10 EST