title: NSun2 Deficiency Protects Endothelium From Inflammation via mRNA Methylation of ICAM-1.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: From 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.).
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Luo
authors.affiliation: From 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.).
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.affiliation: From 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.).
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.affiliation: From 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.). xwang@bjmu.edu.cn wwg@bjmu.edu.cn.
authors.forename: Wengong
authors.initials: W
authors.lastname: Wang
authors.affiliation: From 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.). xwang@bjmu.edu.cn wwg@bjmu.edu.cn.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D055786:Gene Knockout Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000172:deficiency*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D008780:Methyltransferases; C513146:Misu protein, mouse
keywords: NSun2; arteriosclerosis; inflammation; intercellular adhesion molecule-1; methylation