title: Regulation of non-coding RNA networks in the nervous system--what's the REST of the story?
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.
authors.affiliation: Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Irfan A
authors.initials: IA
authors.lastname: Qureshi
authors.forename: Mark F
authors.initials: MF
authors.lastname: Mehler
mesh_terms: D000818:Animals; D006801:Humans; D009420:Nervous System / Q000378:metabolism*; D009422:Nervous System Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D022661:RNA, Untranslated; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor
references.citation: J Biol Chem. 2000 Mar 31;275(13):9461-7
references.pmid: 10734093
references.citation: J Mol Endocrinol. 2008 Apr;40(4):151-9
references.pmid: 18372404
references.citation: J Neurochem. 2008 May;105(4):1369-83
references.pmid: 18298477
references.citation: Cell Cycle. 2006 Sep;5(17):1929-35
references.pmid: 16929174
references.citation: Nat Cell Biol. 2008 Dec;10(12):1470-6
references.pmid: 19011622
references.citation: Genome Res. 2008 Sep;18(9):1433-45
references.pmid: 18562676
references.citation: J Biol Chem. 2008 Dec 12;283(50):34880-6
references.pmid: 18922795
references.citation: Prog Neurobiol. 2008 Dec 11;86(4):305-41
references.pmid: 18940229
references.citation: Mol Cell Biol. 2006 Mar;26(5):1666-78
references.pmid: 16478988
references.citation: Genome Biol. 2009;10(4):R40
references.pmid: 19374775
references.citation: Curr Biol. 2002 Jan 8;12(1):13-25
references.pmid: 11790299
references.citation: Science. 2008 Dec 12;322(5908):1717-20
references.pmid: 18988810
references.citation: J Neurosci. 2008 Oct 15;28(42):10720-33
references.pmid: 18923047
references.citation: Mol Cell. 2009 Mar 27;33(6):717-26
references.pmid: 19217333
references.citation: Neuron. 2001 Aug 16;31(3):353-65
references.pmid: 11516394
references.citation: J Neurosci. 2008 Dec 31;28(53):14341-6
references.pmid: 19118166
references.citation: Mol Cancer Ther. 2005 Mar;4(3):343-9
references.pmid: 15767543
references.citation: Curr Biol. 2005 Sep 6;15(17):R665-8
references.pmid: 16139198
references.citation: Biochem Biophys Res Commun. 2002 Jan 11;290(1):415-20
references.pmid: 11779185
references.citation: Neurobiol Dis. 2008 Mar;29(3):438-45
references.pmid: 18082412
references.citation: J Neurosci. 2003 Mar 15;23(6):2112-21
references.pmid: 12657670
references.citation: Dev Biol. 2007 Feb 1;302(1):1-12
references.pmid: 16989803
references.citation: Biol Direct. 2007 Nov 30;2:35
references.pmid: 18053135
references.citation: Curr Opin Neurobiol. 2005 Oct;15(5):500-6
references.pmid: 16150588
references.citation: PLoS One. 2008;3(11):e3656
references.pmid: 18987749
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):716-21
references.pmid: 18184812
references.citation: Biochem Biophys Res Commun. 2008 Jun 6;370(3):473-7
references.pmid: 18387358
references.citation: Nature. 2007 Jun 14;447(7146):799-816
references.pmid: 17571346
references.citation: Acta Neuropathol. 2006 Oct;112(4):483-90
references.pmid: 16823502
references.citation: RNA. 2009 Jan;15(1):85-96
references.pmid: 19050060
references.citation: Biochem J. 2008 Sep 15;414(3):327-41
references.pmid: 18717648
references.citation: Nature. 2008 May 8;453(7192):223-7
references.pmid: 18362916
references.citation: J Neurosci. 2008 Jul 23;28(30):7555-62
references.pmid: 18650333
references.citation: J Neurosci. 2007 Jun 27;27(26):6972-83
references.pmid: 17596446
references.citation: J Mol Neurosci. 2000 Dec;15(3):205-14
references.pmid: 11303784
references.citation: Nat Neurosci. 2006 Nov;9(11):1382-7
references.pmid: 17041593
references.citation: Stem Cells. 2007 Jan;25(1):2-9
references.pmid: 17023513
references.citation: Brain Pathol. 2010 Jan;20(1):96-105
references.pmid: 19134002
references.citation: Cell. 2005 Jun 17;121(6):837-48
references.pmid: 15960972
references.citation: Neuroscientist. 2008 Oct;14(5):434-45
references.pmid: 18997122
references.citation: Science. 1995 Mar 3;267(5202):1360-3
references.pmid: 7871435
references.citation: Cancer Res. 2000 Apr 1;60(7):1840-4
references.pmid: 10766169
references.citation: Biochem Biophys Res Commun. 2008 Dec 26;377(4):1031-5
references.pmid: 18854179
references.citation: Brain Pathol. 2008 Jan;18(1):122-9
references.pmid: 18226107
references.citation: Nucleic Acids Res. 2006;34(22):6392-403
references.pmid: 17130167
references.citation: Biochim Biophys Acta. 2008 Oct;1783(10):1835-46
references.pmid: 18657578
references.citation: Mol Cell Biol. 2003 Dec;23(24):9025-31
references.pmid: 14645515
references.citation: Cancer Cell. 2008 May;13(5):381-3
references.pmid: 18455121
references.citation: Neurosci Lett. 2006 May 8;398(3):161-6
references.pmid: 16442230
references.citation: Cell. 2001 Aug 24;106(4):465-75
references.pmid: 11525732
references.citation: Am J Hum Genet. 2006 Aug;79(2):370-7
references.pmid: 16826528
references.citation: Nature. 2007 May 31;447(7144):601-5
references.pmid: 17468742
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9873-8
references.pmid: 10449787
references.citation: Science. 2005 Sep 2;309(5740):1559-63
references.pmid: 16141072
references.citation: Nat Genet. 1998 Oct;20(2):136-42
references.pmid: 9771705
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10820-5
references.pmid: 18669659
references.citation: Nature. 2009 Feb 26;457(7233):E4-5; discussion E7
references.pmid: 19242417
references.citation: Bioessays. 2009 Jan;31(1):51-9
references.pmid: 19154003
references.citation: Mamm Genome. 2008 Aug;19(7-8):454-92
references.pmid: 18839252
references.citation: Genome Res. 2006 Oct;16(10):1208-21
references.pmid: 16963704
references.citation: Mol Cell. 2008 Aug 8;31(3):347-59
references.pmid: 18691967
references.citation: Mol Cell. 2007 Aug 3;27(3):435-48
references.pmid: 17679093
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4170-5
references.pmid: 17360495
references.citation: Hum Mol Genet. 2009 Apr 15;18(8):1405-14
references.pmid: 19218269
references.citation: Brain Res Mol Brain Res. 1999 Sep 8;72(1):30-9
references.pmid: 10521596
references.citation: Nat Cell Biol. 2007 Jun;9(6):654-9
references.pmid: 17486113
references.citation: Cancer Biol Ther. 2008 Sep;7(9):1326-34
references.pmid: 18836290
references.citation: Nature. 2008 Mar 20;452(7185):370-4
references.pmid: 18354483
references.citation: Brain Res Mol Brain Res. 2000 Aug 14;80(1):88-98
references.pmid: 11039732
references.citation: J Biol Chem. 2009 Jan 30;284(5):2648-2656
references.pmid: 19049968
references.citation: Am J Hum Genet. 2008 Nov;83(5):572-81
references.pmid: 18976727
references.citation: Genome Res. 2009 Jun;19(6):994-1005
references.pmid: 19401398
references.citation: Cell. 2005 May 20;121(4):645-657
references.pmid: 15907476
references.citation: BMB Rep. 2009 Jan 31;42(1):6-15
references.pmid: 19192387
references.citation: Nucleic Acids Symp Ser (Oxf). 2005;(49):87-8
references.pmid: 17150646
references.citation: Mol Cell Biol. 1999 Oct;19(10):6788-95
references.pmid: 10490617
references.citation: Genome Biol. 2006;7(9):R85
references.pmid: 17002790
references.citation: Nat Med. 2000 Jul;6(7):826-31
references.pmid: 10888935
references.citation: Genome Biol. 2009;10(1):R9
references.pmid: 19173732
references.citation: Brain Res Mol Brain Res. 2001 Jun 20;90(2):174-86
references.pmid: 11406295
references.citation: J Neurosci. 2007 Jun 20;27(25):6729-39
references.pmid: 17581960
references.citation: J Physiol. 2006 Sep 1;575(Pt 2):319-20
references.pmid: 16887869
references.citation: Nature. 2009 Feb 26;457(7233):E5-6; discussion E7
references.pmid: 19242418
references.citation: Development. 2009 Mar;136(5):715-21
references.pmid: 19201947
references.citation: Science. 2007 Jun 8;316(5830):1497-502
references.pmid: 17540862
references.citation: Nature. 2008 Mar 20;452(7185):365-9
references.pmid: 18354482
references.citation: J Med Genet. 2009 Sep;46(9):598-606
references.pmid: 19264732
references.citation: Biochem Biophys Res Commun. 2003 Nov 7;311(1):55-63
references.pmid: 14575694
references.citation: PLoS Biol. 2008 Oct 28;6(10):e256
references.pmid: 18959480
references.citation: Cell. 2004 Mar 19;116(6):779-93
references.pmid: 15035981
references.citation: Am J Hum Genet. 2008 Sep;83(3):388-400
references.pmid: 18771760
references.citation: J Neurochem. 2006 Feb;96(4):1130-8
references.pmid: 16417580
references.citation: RNA Biol. 2008 Oct-Dec;5(4):244-8
references.pmid: 19182533
references.citation: PLoS One. 2008;3(11):e3694
references.pmid: 19002258
references.citation: Biol Cell. 2009 Mar;101(3):169-81
references.pmid: 19152504
references.citation: Nat Rev Genet. 2007 Jul;8(7):544-54
references.pmid: 17572692
references.citation: Mol Cell Biol. 2004 Jan;24(1):442-53
references.pmid: 14673176
references.citation: Ann N Y Acad Sci. 2009 Jan;1152:194-200
references.pmid: 19161390
references.citation: Mol Cell. 2008 Dec 5;32(5):718-26
references.pmid: 19061646
references.citation: Genes Dev. 2007 Apr 1;21(7):744-9
references.pmid: 17403776
references.citation: J Physiol. 2006 Sep 1;575(Pt 2):321-32
references.pmid: 16857706