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Chromatin target of protein arginine methyltransferases alleviates cerebral ischemia/reperfusion-induced injury by regulating RNA alternative splicing

Authors :
Yu Cui
Zhaolong Zhang
Mengfei Lv
Zhongying Duan
Wenhao Liu
Jingchen Gao
Rui Xu
Qi Wan
Source :
iScience, Vol 27, Iss 1, Pp 108688- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: RNA splicing is a post-transcriptional event that regulates many physiological and pathological events. However, whether RNA splicing regulates cerebral I/R-induced brain injury remains largely unknown. In this study, we found that the chromatin target of Prmts (CHTOP) was highly expressed in neurons, and anti-inflammatory cytokine interleukin-10 (IL-10) upregulates its expression after ischemia. In addition, overexpression or knockdown of CHTOP alleviated or exacerbated neuronal death in both experimental stroke mice and cultured neurons. Mechanistically, RNA alternative splicing is altered early after oxygen and glucose deprivation/reoxygenation (OGD/R). CHTOP interacted with nuclear speckle-related proteins to regulate alternative mRNA splicing of neuronal survival-related genes after OGD/R. In addition, I/R injury-induced cytokines IL-10 regulate CHTOP-mediated RNA splicing to alleviate ischemic brain injury. Taken together, this study reveals the alteration of RNA splicing after OGD/R and identifies the IL-10-CHTOP-RNA splicing axis as a modulator of brain injury, which may be promising therapeutic targets for ischemic stroke.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
1
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.120e0e38785f4b428f5303bf5b4a457a
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2023.108688