The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK
The methyltransferase SETD3 is an enzyme essential for catalyzing histidine-73 methylation on β-Actin, thereby promoting its polymerization and regulating muscle contraction. Although increasing evidence suggests that SETD3 is involved in multiple physiological or pathological events, its biological...
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| Format: | Article |
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Elsevier
2024-12-01
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| Series: | Cell Insight |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772892724000531 |
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| author | Yue-Yu Kong Wen-Jie Shu Shuang Wang Zhao-Hong Yin Hongguo Duan Ke Li Hai-Ning Du |
| author_facet | Yue-Yu Kong Wen-Jie Shu Shuang Wang Zhao-Hong Yin Hongguo Duan Ke Li Hai-Ning Du |
| author_sort | Yue-Yu Kong |
| collection | DOAJ |
| description | The methyltransferase SETD3 is an enzyme essential for catalyzing histidine-73 methylation on β-Actin, thereby promoting its polymerization and regulating muscle contraction. Although increasing evidence suggests that SETD3 is involved in multiple physiological or pathological events, its biological functions remain incompletely understood. In this study, we utilize in situ proximity labeling combined with mass spectrometry analysis to detect potential interacting partners of SETD3. Unexpectedly, we find that many splicing factors are associated with SETD3. Genome-wide RNA sequencing reveals that SETD3 regulates pre-mRNA splicing events, predominantly influencing exon skipping. Biochemical and bioinformatic analyses suggest that SETD3 interacts with hnRNPK, and they collaboratively regulate exon skipping in a common subset of genes. Functionally, we demonstrate that SETD3 and hnRNPK are required for retention of exon 7 skipping in the FNIP1 gene. This promotes FNIP1-mediated nuclear translocation of the transcription factor TFEB and the subsequent induction of lysosomal and mitochondrial biogenesis. Overall, this study uncovers a novel function of SETD3 in modulating mRNA exon splicing. |
| format | Article |
| id | doaj-art-d3ccfd0169af4e2e8a3b3900c6183d37 |
| institution | Kabale University |
| issn | 2772-8927 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Insight |
| spelling | doaj-art-d3ccfd0169af4e2e8a3b3900c6183d372024-11-10T04:07:53ZengElsevierCell Insight2772-89272024-12-0136100198The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPKYue-Yu Kong0Wen-Jie Shu1Shuang Wang2Zhao-Hong Yin3Hongguo Duan4Ke Li5Hai-Ning Du6Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, ChinaSchool of Basic Medical Sciences, Xi'an JiaoTong University, Xi'an, 710049, ChinaHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, ChinaHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, ChinaHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, ChinaHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, ChinaHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, China; Corresponding author.The methyltransferase SETD3 is an enzyme essential for catalyzing histidine-73 methylation on β-Actin, thereby promoting its polymerization and regulating muscle contraction. Although increasing evidence suggests that SETD3 is involved in multiple physiological or pathological events, its biological functions remain incompletely understood. In this study, we utilize in situ proximity labeling combined with mass spectrometry analysis to detect potential interacting partners of SETD3. Unexpectedly, we find that many splicing factors are associated with SETD3. Genome-wide RNA sequencing reveals that SETD3 regulates pre-mRNA splicing events, predominantly influencing exon skipping. Biochemical and bioinformatic analyses suggest that SETD3 interacts with hnRNPK, and they collaboratively regulate exon skipping in a common subset of genes. Functionally, we demonstrate that SETD3 and hnRNPK are required for retention of exon 7 skipping in the FNIP1 gene. This promotes FNIP1-mediated nuclear translocation of the transcription factor TFEB and the subsequent induction of lysosomal and mitochondrial biogenesis. Overall, this study uncovers a novel function of SETD3 in modulating mRNA exon splicing.http://www.sciencedirect.com/science/article/pii/S2772892724000531SETD3RNA splicingRBPshnRNPKFNIP1 |
| spellingShingle | Yue-Yu Kong Wen-Jie Shu Shuang Wang Zhao-Hong Yin Hongguo Duan Ke Li Hai-Ning Du The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK Cell Insight SETD3 RNA splicing RBPs hnRNPK FNIP1 |
| title | The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK |
| title_full | The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK |
| title_fullStr | The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK |
| title_full_unstemmed | The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK |
| title_short | The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK |
| title_sort | methyltransferase setd3 regulates mrna alternative splicing through interacting with hnrnpk |
| topic | SETD3 RNA splicing RBPs hnRNPK FNIP1 |
| url | http://www.sciencedirect.com/science/article/pii/S2772892724000531 |
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