A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice
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...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/12/6584 |
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| author | Wen Wang Hengjun Huang Hao Jiang Chi Tian Yisen Tang Diwen Gan Xiaozhen Wen Zhenyu Song Yuhao He Xijun Ou Liang Fang |
| author_facet | Wen Wang Hengjun Huang Hao Jiang Chi Tian Yisen Tang Diwen Gan Xiaozhen Wen Zhenyu Song Yuhao He Xijun Ou Liang Fang |
| author_sort | Wen Wang |
| collection | DOAJ |
| description | 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:35:04Z |
| publishDate | 2022-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5f27ba9de95b4db884406fdf2b7f29bc2023-11-23T17:03:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312658410.3390/ijms23126584A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout MiceWen Wang0Hengjun Huang1Hao Jiang2Chi Tian3Yisen Tang4Diwen Gan5Xiaozhen Wen6Zhenyu Song7Yuhao He8Xijun Ou9Liang Fang10Harbin Institute of Technology, Harbin 150001, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaDepartment of Biology, Southern University of Science and Technology, Shenzhen 518005, ChinaThe 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.https://www.mdpi.com/1422-0067/23/12/6584Nsun65-methylcytosineknockout mousephenotype |
| spellingShingle | Wen Wang Hengjun Huang Hao Jiang Chi Tian Yisen Tang Diwen Gan Xiaozhen Wen Zhenyu Song Yuhao He Xijun Ou Liang Fang A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice International Journal of Molecular Sciences Nsun6 5-methylcytosine knockout mouse phenotype |
| title | A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice |
| title_full | A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice |
| title_fullStr | A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice |
| title_full_unstemmed | A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice |
| title_short | A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice |
| title_sort | cross tissue investigation of molecular targets and physiological functions of nsun6 using knockout mice |
| topic | Nsun6 5-methylcytosine knockout mouse phenotype |
| url | https://www.mdpi.com/1422-0067/23/12/6584 |
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