GlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidum
Abstract PRMT5, a type II arginine methyltransferase, is involved in transcriptional regulation, RNA processing and other biological processes and signal transduction. Secondary metabolites are vital pharmacological compounds in Ganoderma lucidum, and their content is an important indicator for eval...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-05942-y |
| _version_ | 1797273570123972608 |
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| author | Zi Wang Hao Qiu Yefan Li Mingwen Zhao Rui Liu |
| author_facet | Zi Wang Hao Qiu Yefan Li Mingwen Zhao Rui Liu |
| author_sort | Zi Wang |
| collection | DOAJ |
| description | Abstract PRMT5, a type II arginine methyltransferase, is involved in transcriptional regulation, RNA processing and other biological processes and signal transduction. Secondary metabolites are vital pharmacological compounds in Ganoderma lucidum, and their content is an important indicator for evaluating the quality of G. lucidum. Here, we found that GlPRMT5 negatively regulates the biosynthesis of secondary metabolites. In further in-depth research, GlPP2C1 (a type 2C protein phosphatase) was identified out as an interacting protein of GlPRMT5 by immunoprecipitation-mass spectrometry (IP-MS). Further mass spectrometry detection revealed that GlPRMT5 symmetrically dimethylates the arginine 99 (R99) and arginine 493 (R493) residues of GlPP2C1 to weaken its activity. The symmetrical dimethylation modification of the R99 residue is the key to affecting GlPP2C1 activity. Symmetrical demethylation-modified GlPP2C1 does not affect the interaction with GlPRMT5. In addition, silencing GlPP2C1 clearly reduced GA content, indicating that GlPP2C1 positively regulates the biosynthesis of secondary metabolites in G. lucidum. In summary, this study reveals the molecular mechanism by which GlPRMT5 regulates secondary metabolites, and these studies provide further insights into the target proteins of GlPRMT5 and symmetric dimethylation sites. Furthermore, these studies provide a basis for the mutual regulation between different epigenetic modifications. |
| first_indexed | 2024-03-07T14:46:17Z |
| format | Article |
| id | doaj.art-00ed4c54ddef4e5a858cf1ee4d0571b6 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-07T14:46:17Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-00ed4c54ddef4e5a858cf1ee4d0571b62024-03-05T19:59:05ZengNature PortfolioCommunications Biology2399-36422024-02-017111210.1038/s42003-024-05942-yGlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidumZi Wang0Hao Qiu1Yefan Li2Mingwen Zhao3Rui Liu4Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture and Rural Affairs; Microbiology Department, College of Life Sciences, Nanjing Agricultural UniversityKey Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture and Rural Affairs; Microbiology Department, College of Life Sciences, Nanjing Agricultural UniversityKey Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture and Rural Affairs; Microbiology Department, College of Life Sciences, Nanjing Agricultural UniversityKey Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture and Rural Affairs; Microbiology Department, College of Life Sciences, Nanjing Agricultural UniversityKey Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture and Rural Affairs; Microbiology Department, College of Life Sciences, Nanjing Agricultural UniversityAbstract PRMT5, a type II arginine methyltransferase, is involved in transcriptional regulation, RNA processing and other biological processes and signal transduction. Secondary metabolites are vital pharmacological compounds in Ganoderma lucidum, and their content is an important indicator for evaluating the quality of G. lucidum. Here, we found that GlPRMT5 negatively regulates the biosynthesis of secondary metabolites. In further in-depth research, GlPP2C1 (a type 2C protein phosphatase) was identified out as an interacting protein of GlPRMT5 by immunoprecipitation-mass spectrometry (IP-MS). Further mass spectrometry detection revealed that GlPRMT5 symmetrically dimethylates the arginine 99 (R99) and arginine 493 (R493) residues of GlPP2C1 to weaken its activity. The symmetrical dimethylation modification of the R99 residue is the key to affecting GlPP2C1 activity. Symmetrical demethylation-modified GlPP2C1 does not affect the interaction with GlPRMT5. In addition, silencing GlPP2C1 clearly reduced GA content, indicating that GlPP2C1 positively regulates the biosynthesis of secondary metabolites in G. lucidum. In summary, this study reveals the molecular mechanism by which GlPRMT5 regulates secondary metabolites, and these studies provide further insights into the target proteins of GlPRMT5 and symmetric dimethylation sites. Furthermore, these studies provide a basis for the mutual regulation between different epigenetic modifications.https://doi.org/10.1038/s42003-024-05942-y |
| spellingShingle | Zi Wang Hao Qiu Yefan Li Mingwen Zhao Rui Liu GlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidum Communications Biology |
| title | GlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidum |
| title_full | GlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidum |
| title_fullStr | GlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidum |
| title_full_unstemmed | GlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidum |
| title_short | GlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidum |
| title_sort | glprmt5 inhibits glpp2c1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in ganoderma lucidum |
| url | https://doi.org/10.1038/s42003-024-05942-y |
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