Downregulation of a Dorsal Root Ganglion-Specifically Enriched Long Noncoding RNA is Required for Neuropathic Pain by Negatively Regulating RALY-Triggered Ehmt2 Expression.
DRG‐specifically enriched long noncoding RNA
Dorsal root ganglion
Ehmt2
G9a
Neuropathic pain
RALY
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
19
03
2021
received:
23
11
2020
entrez:
12
8
2021
pubmed:
13
8
2021
medline:
6
1
2022
Statut:
ppublish
Résumé
Nerve injury-induced maladaptive changes of gene expression in dorsal root ganglion (DRG) neurons contribute to neuropathic pain. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression. Here, a conserved lncRNA is reported, named DRG-specifically enriched lncRNA (DS-lncRNA) for its high expression in DRG neurons. Peripheral nerve injury downregulates DS-lncRNA in injured DRG due, in part, to silencing of POU domain, class 4, transcription factor 3, a transcription factor that interacts with the DS-lncRNA gene promoter. Rescuing DS-lncRNA downregulation blocks nerve injury-induced increases in the transcriptional cofactor RALY-triggered DRG Ehmt2 mRNA and its encoding G9a protein, reverses the G9a-controlled downregulation of opioid receptors and Kcna2 in injured DRG, and attenuates nerve injury-induced pain hypersensitivities in male mice. Conversely, DS-lncRNA downregulation increases RALY-triggered Ehmt2/G9a expression and correspondingly decreases opioid receptor and Kcna2 expression in DRG, leading to neuropathic pain symptoms in male mice in the absence of nerve injury. Mechanistically, downregulated DS-lncRNA promotes more binding of increased RALY to RNA polymerase II and the Ehmt2 gene promoter and enhances Ehmt2 transcription in injured DRG. Thus, downregulation of DS-lncRNA likely contributes to neuropathic pain by negatively regulating the expression of RALY-triggered Ehmt2/G9a, a key neuropathic pain player, in DRG neurons.
Identifiants
pubmed: 34383386
doi: 10.1002/advs.202004515
pmc: PMC8356248
doi:
Substances chimiques
Heterogeneous-Nuclear Ribonucleoprotein Group C
0
RNA, Long Noncoding
0
Raly protein, mouse
0
G9a protein, mouse
EC 2.1.1.43
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2004515Subventions
Organisme : NIH HHS
ID : RFNS113881
Pays : United States
Organisme : NIH HHS
ID : R01NS117484
Pays : United States
Organisme : NIH HHS
ID : 1S10OD025047-01
Pays : United States
Organisme : NIH HHS
ID : NS046593
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS117484
Pays : United States
Organisme : NIH HHS
ID : S10 OD025047
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS111553
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS046593
Pays : United States
Organisme : NIH HHS
ID : R01NS111553
Pays : United States
Informations de copyright
© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.
Références
Sci Signal. 2017 Jul 11;10(487):
pubmed: 28698219
Cell. 2013 Jul 3;154(1):26-46
pubmed: 23827673
Adv Sci (Weinh). 2021 Jul;8(13):e2004515
pubmed: 34383386
Nat Commun. 2020 Feb 20;11(1):984
pubmed: 32080181
Transl Perioper Pain Med. 2019;6(4):106-114
pubmed: 31497620
Gerontology. 2013;59(6):524-33
pubmed: 24008580
Genes Dev. 2011 Apr 15;25(8):781-8
pubmed: 21498567
Exp Brain Res. 2009 Jun;196(1):115-28
pubmed: 19242687
Pain. 2017 Jun;158(6):1153-1165
pubmed: 28267064
Neuroscience. 2000;98(2):201-6
pubmed: 10854750
J Neurosci. 2012 Jan 18;32(3):995-1007
pubmed: 22262898
Methods Mol Med. 2001;51:205-13
pubmed: 21331717
Cell. 2007 Feb 23;128(4):693-705
pubmed: 17320507
Anesthesiology. 2014 Aug;121(2):409-17
pubmed: 24739997
Expert Opin Ther Targets. 2019 Jan;23(1):15-20
pubmed: 30451044
Pain Pract. 2002 Jun;2(2):87-97
pubmed: 17147683
Nat Commun. 2017 Mar 08;8:14712
pubmed: 28270689
Mol Pain. 2011 Feb 23;7:16
pubmed: 21345196
Mol Pain. 2016 Mar 11;12:
pubmed: 27030721
Nat Protoc. 2012 Jul 26;7(8):1534-50
pubmed: 22836135
Pain. 2018 Jul;159(7):1325-1345
pubmed: 29561359
Nature. 2014 Jan 30;505(7485):635-40
pubmed: 24463510
Transl Perioper Pain Med. 2020;7(2):176-184
pubmed: 32099850
Pharmacoeconomics. 2009;27(2):95-112
pubmed: 19254044
Neuron. 2006 Oct 5;52(1):77-92
pubmed: 17015228
J Neurosci. 2019 Aug 14;39(33):6595-6607
pubmed: 31182635
Behav Neurol. 2017;2017:2941297
pubmed: 28928602
J Clin Invest. 2014 Feb;124(2):592-603
pubmed: 24382350
Genome Res. 2014 Apr;24(4):616-28
pubmed: 24429298
Bioinformatics. 2011 Jul 1;27(13):i275-82
pubmed: 21685081
Pain. 2019 Feb;160(2):375-384
pubmed: 30247265
Mol Neurobiol. 2017 Jan;54(1):511-523
pubmed: 26742527
Purinergic Signal. 2016 Mar;12(1):139-48
pubmed: 26686228
Nature. 2016 May 11;534(7605):124-8
pubmed: 27251289
J Virol. 2006 Jul;80(13):6669-77
pubmed: 16775354
J Neurosci. 2009 Mar 11;29(10):3206-19
pubmed: 19279258
Sci Rep. 2016 Nov 22;6:37704
pubmed: 27874088
Neurotherapeutics. 2019 Apr;16(2):491-504
pubmed: 30515739
Biomed Res Int. 2017;2017:7831251
pubmed: 29204447
Int J Mol Med. 2018 Aug;42(2):1152-1160
pubmed: 29750294
Anat Rec (Hoboken). 2011 Aug;294(8):1406-11
pubmed: 21714116
J Biol Chem. 2016 Apr 15;291(16):8475-85
pubmed: 26917724
Mol Brain. 2016 Apr 23;9:44
pubmed: 27107575
Cell. 2008 Nov 28;135(5):919-32
pubmed: 19041754
Mayo Clin Proc. 2015 Apr;90(4):532-45
pubmed: 25841257
Nat Genet. 2011 Jun 05;43(7):621-9
pubmed: 21642992
Neuroscience. 2018 Mar 15;374:214-222
pubmed: 29421435
Pain. 2014 Apr;155(4):654-662
pubmed: 24291734
Mol Med Rep. 2018 Apr;17(4):5851-5859
pubmed: 29436679
Cell. 2015 Apr 9;161(2):404-16
pubmed: 25843628
J Neurosci. 2003 Jul 30;23(17):6703-12
pubmed: 12890763
FEBS Lett. 2018 Sep;592(17):2884-2900
pubmed: 29972883
Nat Neurosci. 2015 Dec;18(12):1746-55
pubmed: 26551542
Int J Biochem Cell Biol. 2014 Sep;54:331-7
pubmed: 24993078
Pain Manag Nurs. 2004 Dec;5(4 Suppl 1):3-8
pubmed: 15644854
Pain. 2008 May;136(1-2):188-201
pubmed: 18316160
Pain. 2015 Apr;156(4):711-721
pubmed: 25630025
Nat Neurosci. 2013 Aug;16(8):1024-31
pubmed: 23792947
Adv Sci (Weinh). 2020 May 27;7(13):1902402
pubmed: 32670741
J Vis Exp. 2012 Mar 25;(61):
pubmed: 22472705
Epigenomics. 2015;7(2):235-45
pubmed: 25942533
Mol Pain. 2014 Jan 29;10:8
pubmed: 24472174