Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis
Type I interferon and apoptosis elicit multifaceted effects on host defense and various diseases, such as viral infections and cancers. However, the gene/protein network regulating type I interferon and apoptosis has not been elucidated completely. In this study, we selected grass carp (Ctenopharyng...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.762162/full |
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| author | Zhi-Chao Sun Zhi-Chao Sun Zhi-Chao Sun Zeyin Jiang Xiaowen Xu Meifeng Li Qing Zeng Ying Zhu Ying Zhu Ying Zhu Ying Zhu Shanghong Wang Yuanyuan Li Xiao-Li Tian Xiao-Li Tian Xiao-Li Tian Chengyu Hu |
| author_facet | Zhi-Chao Sun Zhi-Chao Sun Zhi-Chao Sun Zeyin Jiang Xiaowen Xu Meifeng Li Qing Zeng Ying Zhu Ying Zhu Ying Zhu Ying Zhu Shanghong Wang Yuanyuan Li Xiao-Li Tian Xiao-Li Tian Xiao-Li Tian Chengyu Hu |
| author_sort | Zhi-Chao Sun |
| collection | DOAJ |
| description | Type I interferon and apoptosis elicit multifaceted effects on host defense and various diseases, such as viral infections and cancers. However, the gene/protein network regulating type I interferon and apoptosis has not been elucidated completely. In this study, we selected grass carp (Ctenopharyngodon idella) as an experimental model to investigate the modulation of RNASEK on the secretion of type I interferon and apoptosis. We first cloned two paralogs RNASEK-a and -b in grass carp, defined three exons in each gene, and found the length of both coding regions is 306 bp with 73.27% of protein homology. The protein sequences of the two paralogs are highly conserved across species. Two proteins were mainly localized in early and late endosomes and endoplasmic reticulum. Further, quantitative real-time PCR demonstrated that dsRNA poly I:C and grass carp reovirus upregulated RNASEK-a and -b in grass carp cells and tissues. Overexpression of RNASEK-a and -b individually induced type I interferon expression and the phosphorylation of IRF3/IRF7 shown by Western blot and immunofluorescent staining, increased Bax/Bcl-2 mRNA ratio, DNA fragmentations, TUNEL-positive cells, and the proportion of Annexin V-positive signals in flow cytometry, and activated eIF2α, opposite to that observed when RNASEK-a and -b were knocked down in multiple cell types. Taken together, we claim for the first time that fish paralog proteins RNASEK-a and -b enhance type I interferon secretion and promote apoptosis, which may be involved in the phosphorylation of IRF3/IRF7 and eIF2α, respectively. Our study reveals a previously unrecognized role of RNASEK as a new positive regulator of type I interferon and apoptosis. |
| first_indexed | 2024-12-14T07:03:15Z |
| format | Article |
| id | doaj.art-1f962980d9a44694bfd71a0814e081b3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T07:03:15Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1f962980d9a44694bfd71a0814e081b32022-12-21T23:12:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.762162762162Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote ApoptosisZhi-Chao Sun0Zhi-Chao Sun1Zhi-Chao Sun2Zeyin Jiang3Xiaowen Xu4Meifeng Li5Qing Zeng6Ying Zhu7Ying Zhu8Ying Zhu9Ying Zhu10Shanghong Wang11Yuanyuan Li12Xiao-Li Tian13Xiao-Li Tian14Xiao-Li Tian15Chengyu Hu16College of Life Science, Nanchang University, Nanchang, ChinaHuman Aging Research Institute, Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang, ChinaCollege of Life Science, Nanchang University, Nanchang, ChinaCollege of Life Science, Nanchang University, Nanchang, ChinaCollege of Life Science, Nanchang University, Nanchang, ChinaCollege of Life Science, Nanchang University, Nanchang, ChinaCollege of Life Science, Nanchang University, Nanchang, ChinaHuman Aging Research Institute, Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang, ChinaBlood Transfusion Department, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaCollege of Life Science, Nanchang University, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaCollege of Life Science, Nanchang University, Nanchang, ChinaHuman Aging Research Institute, Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang, ChinaCollege of Life Science, Nanchang University, Nanchang, ChinaType I interferon and apoptosis elicit multifaceted effects on host defense and various diseases, such as viral infections and cancers. However, the gene/protein network regulating type I interferon and apoptosis has not been elucidated completely. In this study, we selected grass carp (Ctenopharyngodon idella) as an experimental model to investigate the modulation of RNASEK on the secretion of type I interferon and apoptosis. We first cloned two paralogs RNASEK-a and -b in grass carp, defined three exons in each gene, and found the length of both coding regions is 306 bp with 73.27% of protein homology. The protein sequences of the two paralogs are highly conserved across species. Two proteins were mainly localized in early and late endosomes and endoplasmic reticulum. Further, quantitative real-time PCR demonstrated that dsRNA poly I:C and grass carp reovirus upregulated RNASEK-a and -b in grass carp cells and tissues. Overexpression of RNASEK-a and -b individually induced type I interferon expression and the phosphorylation of IRF3/IRF7 shown by Western blot and immunofluorescent staining, increased Bax/Bcl-2 mRNA ratio, DNA fragmentations, TUNEL-positive cells, and the proportion of Annexin V-positive signals in flow cytometry, and activated eIF2α, opposite to that observed when RNASEK-a and -b were knocked down in multiple cell types. Taken together, we claim for the first time that fish paralog proteins RNASEK-a and -b enhance type I interferon secretion and promote apoptosis, which may be involved in the phosphorylation of IRF3/IRF7 and eIF2α, respectively. Our study reveals a previously unrecognized role of RNASEK as a new positive regulator of type I interferon and apoptosis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.762162/fullRNASEK-aRNASEK-bCtenopharyngodon idellatype I interferonapoptosis |
| spellingShingle | Zhi-Chao Sun Zhi-Chao Sun Zhi-Chao Sun Zeyin Jiang Xiaowen Xu Meifeng Li Qing Zeng Ying Zhu Ying Zhu Ying Zhu Ying Zhu Shanghong Wang Yuanyuan Li Xiao-Li Tian Xiao-Li Tian Xiao-Li Tian Chengyu Hu Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis Frontiers in Immunology RNASEK-a RNASEK-b Ctenopharyngodon idella type I interferon apoptosis |
| title | Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis |
| title_full | Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis |
| title_fullStr | Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis |
| title_full_unstemmed | Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis |
| title_short | Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis |
| title_sort | fish paralog proteins rnasek a and b enhance type i interferon secretion and promote apoptosis |
| topic | RNASEK-a RNASEK-b Ctenopharyngodon idella type I interferon apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.762162/full |
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