Long non-coding RNA rhabdomyosarcoma 2-associated transcript contributes to neuropathic pain by recruiting HuR to stabilize DNA methyltransferase 3 alpha mRNA expression in dorsal root ganglion neuron

Long non-coding RNAs (lncRNAs) act as key regulators in multiple human diseases. In particular, the dysfunction of lncRNAs in dorsal root ganglion (DRG) contributes to the pathogenesis of neuropathic pain (NP). Nevertheless, the role and mechanism of most lncRNAs in NP remain unclear. Two classic ch...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in molecular neuroscience 2023-02, Vol.15, p.1027063-1027063
Main Authors: Guo, Xinying, Zhang, Gaolong, Cai, Weihua, Huang, Fa, Qin, Jingwen, Song, Xingrong
Format: Article
Language:English
Subjects:
Activating transcription factor 3
Chronic pain
DNA methylation
DNA methyltransferase
DNA methyltransferase 3 alpha (DNMT3A)
Dorsal root ganglia
Drug development
Gene expression
HuR
HuR protein
Metadata
mRNA stability
Neurons
neuropathic pain
Neuroscience
Non-coding RNA
Peripheral nerves
Peripheral neuropathy
Proteins
Rhabdomyosarcoma
Rmst lncRNA
RNA-binding protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Long non-coding RNAs (lncRNAs) act as key regulators in multiple human diseases. In particular, the dysfunction of lncRNAs in dorsal root ganglion (DRG) contributes to the pathogenesis of neuropathic pain (NP). Nevertheless, the role and mechanism of most lncRNAs in NP remain unclear. Two classic chronic NP models, including L4 spinal nerve ligation (SNL) model and chronic constriction injury (CCI) of the sciatic nerve, were performed. Mechanical allodynia and heat hyperalgesia were used to evaluate neuropathic pain. DRG microinjection was used to deliver agents into DRG. qRT-PCR, immunofluorescence, immunoprecipitation, western blotting, siRNA transfection, AAV transduction were performed to investigate the phenotypes and molecular basis. Here, we discovered that as a lncRNA was specifically expressed in injured DRG neurons and significantly upregulated following peripheral nerve damage. overexpression by direct DRG injection of AAV5- causes neuropathic symptoms in the absence of nerve damage. Conversely, blocking expression in injured DRGs alleviated nerve injury-induced pain hypersensitivities and downregulated expression. Furthermore, we found peripheral nerve damage induced increase could interact with RNA-binding protein HuR to stabilize the mRNA. Our findings reveal a crucial role of in damaged DRG neurons under NP condition and provide a novel target for drug development against NP.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2022.1027063