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Updated: Mar 26, 2026
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
NSun2 Deficiency Protects Endothelium From Inflammation via mRNA Methylation of ICAM-1
Yuhong Luo1, Juan Feng1, Qingbo Xu1
1From the Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, P.R. China (Y.L., J.F., X.W.); Cardiovascular Division, BHF Centre for Vascular Regeneration, King's College London, United Kingdom (Q.X.); and Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing, P.R. China (W.W.).
Rationale:
Vascular endothelial inflammation, including the expression of intercellular adhesion molecule 1 (ICAM-1), is a key event in vascular diseases. However, the mechanisms underlying the regulation of ICAM-1 are largely unknown.
Objective:
To investigate the mechanisms on the regulation of ICAM-1 by NOP2/Sun domain family, member 2 (NSun2)-mediated mRNA methylation and the impact of NSun2-ICAM-1 regulatory process in vascular inflammation and allograft arteriosclerosis.
Methods And Results:
By using in vitro, in cells, and in vivo methylation assays, we showed that the tRNA methyltransferase NSun2 methylated the ICAM-1 mRNA. Methylation by NSun2 promoted the translation of ICAM-1, thereby increasing the adhesion of leukocytes to endothelial cells. Tumor necrosis factor-α or homocysteine activated the methyltransferase activity of NSun2 by repressing the phosphorylation of NSun2 by Aurora-B. The levels of ICAM-1 induction and of leukocyte adhesion to vascular endothelium observed with homocysteine treatment in wild-type rats were markedly decreased in NSun2(-/-) rats. In a rat model of aortic allograft, the lack of donor NSun2 impaired the formation of allograft arteriosclerosis.
Conclusions:
NSun2 upregulates the expression of ICAM-1 by methylating ICAM-1 mRNA. This regulatory process impacts on vascular inflammation and allograft arteriosclerosis.
Insights
The enzyme NSun2 (NOP2/Sun domain family, member 2) upregulates ICAM-1 expression by methylating its mRNA, promoting vascular inflammation and arteriosclerosis. This NSun2-ICAM-1 pathway is a key regulator in vascular disease progression.
Area of Science:
- Molecular Biology
- Biochemistry
- Immunology
Background:
- Vascular endothelial inflammation is critical in cardiovascular diseases.
- Intercellular adhesion molecule 1 (ICAM-1) expression is a key marker.
- Mechanisms regulating ICAM-1 remain largely undefined.
Purpose of the Study:
- To elucidate the role of NSun2 (NOP2/Sun domain family, member 2) in ICAM-1 regulation via mRNA methylation.
- To investigate the impact of the NSun2-ICAM-1 pathway on vascular inflammation.
- To assess the NSun2-ICAM-1 process in allograft arteriosclerosis.
Main Methods:
- In vitro, cellular, and in vivo methylation assays were employed.
- tRNA methyltransferase NSun2's role in ICAM-1 mRNA methylation was analyzed.
- Experiments utilized wild-type and NSun2(-/-) rats, including an aortic allograft model.
Main Results:
- NSun2 directly methylated ICAM-1 mRNA, enhancing its translation and leukocyte adhesion.
- Tumor necrosis factor-α and homocysteine activated NSun2 by inhibiting Aurora-B phosphorylation.
- NSun2 deficiency significantly reduced ICAM-1 induction, leukocyte adhesion, and allograft arteriosclerosis.
Conclusions:
- NSun2 acts as a key regulator, upregulating ICAM-1 expression through mRNA methylation.
- The NSun2-mediated ICAM-1 pathway is integral to vascular inflammation.
- Targeting NSun2 may offer therapeutic strategies for vascular diseases and transplant arteriosclerosis.
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