A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

Wang, Wen1,2; Huang, Hengjun2; Jiang, Hao2; Tian, Chi2; Tang, Yisen2; Gan, Diwen2; Wen, Xiaozhen2; Song, Zhenyu2; He, Yuhao2; Ou, Xijun2; Fang, Liang2,3

2022-06-01

10.3390/ijms23126584

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Impact Factor & Quartile

1422-0067

The 5-methylcytosine (m5C) modification on an mRNA molecule is deposited by Nsun2 and its paralog Nsun6. While the physiological functions of Nsun2 have been carefully studied using gene knockout (KO) mice, the physiological functions of Nsun6 remain elusive. In this study, we generated an Nsun6-KO mouse strain, which exhibited no apparent phenotype in both the development and adult stages as compared to wild-type mice. Taking advantage of this mouse strain, we identified 80 high-confident Nsun6-dependent m5C sites by mRNA bisulfite sequencing in five different tissues and systematically analyzed the transcriptomic phenotypes of Nsun6-KO tissues by mRNA sequencing. Our data indicated that Nsun6 is not required for the homeostasis of these organs under laboratory housing conditions, but its loss may affect immune response in the spleen and oxidoreductive reaction in the liver under certain conditions. Additionally, we further investigated T-cell-dependent B cell activation in KO mice and found that Nsun6 is not essential for the germinal center B cell formation but is associated with the formation of antibody-secreting plasma cells. Finally, we found that Nsun6-mediated m5C modification does not have any evident influence on the stability of Nsun6 target mRNAs, suggesting that Nsun6-KO-induced phenotypes may be associated with other functions of the m5C modification or Nsun6 protein.

Nsun6 5-methylcytosine knockout mouse phenotype

SCI

English

Corresponding

Shenzhen Key Laboratory of Gene Regulation and Systems Biology[ZDSYS20200811144002008] ; Shenzhen Science and Technology Program["KQTD20180411143432337","JCYJ20190809154407564"] ; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions[2021SHIBS0002]

Biochemistry & Molecular Biology ; Chemistry

Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary

WOS:000816269700001

MDPI

CHEMISTRY

Web of Science

1.Harbin Inst Technol, Harbin 150001, Peoples R China
2.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518005, Peoples R China
3.Southern Univ Sci & Technol, Acad Adv Interdisciplinary Studies, Shenzhen 518005, Peoples R China

Wang, Wen,Huang, Hengjun,Jiang, Hao,et al. A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2022,23(12).

Wang, Wen.,Huang, Hengjun.,Jiang, Hao.,Tian, Chi.,Tang, Yisen.,...&Fang, Liang.(2022).A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,23(12).

Wang, Wen,et al."A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23.12(2022).