PMID- 28919411
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20171130
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 493
IP  - 1
DP  - 2017 Nov 4
TI  - Homocysteine upregulates interleukin-17A expression via NSun2-mediated RNA 
      methylation in T lymphocytes.
PG  - 94-99
LID - S0006-291X(17)31840-5 [pii]
LID - 10.1016/j.bbrc.2017.09.069 [doi]
AB  - Interleukin-17A (IL-17A) has been proven to participate in the process of various 
      autoimmune diseases. The elevation of plasma homocysteine (Hcy), known as 
      hyperhomocysteinemia (HHcy), is related to various chronic inflammatory diseases. 
      Though HHcy-induced upregulation of IL-17A expression in T lymphocytes has been 
      examined, the way in which IL-17A is regulated remains unclear. In this study, 
      western blotting assays showed that Hcy (100 muM) upregulated NOP2/Sun domain 
      family, member 2 (NSun2) expression in rat T lymphocytes. HHcy-induced 
      upregulation of IL-17A observed in plasma of wild-type rats was markedly 
      decreased in NSun2(-/-) rats in vivo. Mechanistically, by using in vitro 
      methylation assays and high-performance liquid chromatography-mass spectrum 
      (HPLC-MS) analysis, we showed that the tRNA methyltransferase NSun2 methylated 
      the IL-17A mRNA in an m5C pattern. The results from bisulfite sequencing 
      indicated that NSun2 methylated IL-17A mRNA at cytosine C466 in vitro and 
      in vivo. Furthermore, we analyzed the activity of pGL3-derived reporters bearing 
      IL-17A mRNA fragments and found that methylation by NSun2 promoted the 
      translation of IL-17A. In conclusion, NSun2 mediates HHcy-induced upregulation of 
      IL-17A expression by methylating IL-17A mRNA and promoting its translation in T 
      lymphocytes.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Wang, Nan
AU  - Wang N
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Science, 
      Peking University Health Science Center, Key Laboratory of Molecular 
      Cardiovascular Science, Ministry of Education, 38 Xueyuan Road, Beijing, 100191, 
      PR China.
FAU - Tang, Hao
AU  - Tang H
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Science, Peking University Health Science Center, Beijing Key Laboratory of 
      Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, 
      Beijing, 100191, PR China.
FAU - Wang, Xian
AU  - Wang X
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Science, 
      Peking University Health Science Center, Key Laboratory of Molecular 
      Cardiovascular Science, Ministry of Education, 38 Xueyuan Road, Beijing, 100191, 
      PR China. Electronic address: xwang@bjmu.edu.cn.
FAU - Wang, Wengong
AU  - Wang W
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Science, Peking University Health Science Center, Beijing Key Laboratory of 
      Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, 
      Beijing, 100191, PR China. Electronic address: wwg@bjmu.edu.cn.
FAU - Feng, Juan
AU  - Feng J
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Science, 
      Peking University Health Science Center, Key Laboratory of Molecular 
      Cardiovascular Science, Ministry of Education, 38 Xueyuan Road, Beijing, 100191, 
      PR China. Electronic address: juanfeng@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170915
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Interleukin-17)
RN  - 0 (RNA, Messenger)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.- (NSun2 protein, rat)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Gene Expression Regulation/physiology
MH  - Homocysteine/*metabolism
MH  - Interleukin-17/*metabolism
MH  - Methylation
MH  - Methyltransferases/*genetics/*metabolism
MH  - RNA, Messenger/*genetics/*metabolism
MH  - Rats
MH  - T-Lymphocytes/*metabolism
MH  - Up-Regulation/physiology
OTO - NOTNLM
OT  - Homocysteine (Hcy)
OT  - Interleukin-17A (IL-17A)
OT  - Member 2 (NSun2)
OT  - Methylation
OT  - NOP2/Sun domain family
EDAT- 2017/09/19 06:00
MHDA- 2017/10/24 06:00
CRDT- 2017/09/19 06:00
PHST- 2017/08/18 00:00 [received]
PHST- 2017/09/13 00:00 [accepted]
PHST- 2017/09/19 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
PHST- 2017/09/19 06:00 [entrez]
AID - S0006-291X(17)31840-5 [pii]
AID - 10.1016/j.bbrc.2017.09.069 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Nov 4;493(1):94-99. doi: 
      10.1016/j.bbrc.2017.09.069. Epub 2017 Sep 15.