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\begin{document}

\title{RALY participates in nerve trauma-induced nociceptive hypersensitivity
through triggering eIF4G2 gene expression in primary sensory neurons}



\author[1]{Lina Huang}%
\author[1]{Dilip Sharma}%
\author[1]{Xiaozhou Feng}%
\author[1]{Zhiqiang Pan}%
\author[1]{Shaogen  Wu}%
\author[1]{Daisy Munoz}%
\author[1]{A. Bekker}%
\author[1]{HuiJuan Hu}%
\author[1]{Yuan-Xiang Tao}%
\affil[1]{Rutgers New Jersey Medical School}%


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  \date{May 26, 2024}


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\begin{abstract}
Background and Purpose: Peripheral nerve trauma-induced dysregulation of
pain-associated genes in the primary sensory neurons of dorsal root
ganglion (DRG) contributes to neuropathic pain genesis. RNA-binding
proteins participate in gene transcription. We hypothesized that RALY,
an RNA-binding protein, participated in nerve trauma-induced
dysregulation of DRG pain-associated genes and nociceptive
hypersensitivity. Methods and results: Immunohistochemistry staining
showed that RALY was expressed exclusively in the nuclei of DRG neurons.
Peripheral nerve trauma caused by chronic constriction injury (CCI) of
unilateral sciatic nerve produced time-dependent increases in the levels
of Raly mRNA and RALY protein in injured DRG. Blocking this increase
through DRG microinjection of adeno-associated virus 5 (AAV5)-expressing
Raly shRNA reduced the CCI-induced elevation in the amount of eukaryotic
initiation factor 4 gamma 2 (eIF4G2) mRNA and eIF4G2 protein in injured
DRG and mitigated the development and maintenance of CCI-induced
nociceptive hypersensitivity, without altering basal (acute) response to
noxious stimuli and locomotor activity. Mimicking DRG increased RALY
through DRG microinjection of AAV5 expressing Raly mRNA upregulated the
expression of eIF4G2 mRNA and eIF4G2 protein in the DRG and led to
hypersensitive responses to noxious stimuli in the absence of nerve
trauma. Mechanistically, CCI promoted the binding of RALY to the
promoter of eIF4G2 gene and triggered its transcriptional activity.
Conclusion and Implications: Our findings indicate that RALY
participates in nerve trauma-induced nociceptive hypersensitivity likely
through transcriptionally triggering eIF4G2 expression in the DRG. RALY
may be a potential target in neuropathic pain management.%
\end{abstract}%



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