A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum
Abstract Protein arginine methyltransferases (PRMTs) regulate many important cellular processes, such as transcription and RNA processing in model organisms but their functions in human malaria parasites are not elucidated. Here, we characterize PfPRMT5 in Plasmodium falciparum, which catalyzes symm...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05038-z |
| _version_ | 1797795498207215616 |
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| author | Amuza Byaruhanga Lucky Chengqi Wang Min Liu Xiaoying Liang Hui Min Qi Fan Faiza Amber Siddiqui Swamy Rakesh Adapa Xiaolian Li Rays H. Y. Jiang Xiaoguang Chen Liwang Cui Jun Miao |
| author_facet | Amuza Byaruhanga Lucky Chengqi Wang Min Liu Xiaoying Liang Hui Min Qi Fan Faiza Amber Siddiqui Swamy Rakesh Adapa Xiaolian Li Rays H. Y. Jiang Xiaoguang Chen Liwang Cui Jun Miao |
| author_sort | Amuza Byaruhanga Lucky |
| collection | DOAJ |
| description | Abstract Protein arginine methyltransferases (PRMTs) regulate many important cellular processes, such as transcription and RNA processing in model organisms but their functions in human malaria parasites are not elucidated. Here, we characterize PfPRMT5 in Plasmodium falciparum, which catalyzes symmetric dimethylation of histone H3 at R2 (H3R2me2s) and R8, and histone H4 at R3 in vitro. P fPRMT5 disruption results in asexual stage growth defects primarily due to lower invasion efficiency of the merozoites. Transcriptomic analysis reveals down-regulation of many transcripts related to invasion upon PfPRMT5 disruption, in agreement with H3R2me2s being an active chromatin mark. Genome-wide chromatin profiling detects extensive H3R2me2s marking of genes of different cellular processes, including invasion-related genes in wildtype parasites and PfPRMT5 disruption leads to the depletion of H3R2me2s. Interactome studies identify the association of PfPRMT5 with invasion-related transcriptional regulators such as AP2-I, BDP1, and GCN5. Furthermore, PfPRMT5 is associated with the RNA splicing machinery, and PfPRMT5 disruption caused substantial anomalies in RNA splicing events, including those for invasion-related genes. In summary, PfPRMT5 is critical for regulating parasite invasion and RNA splicing in this early-branching eukaryote. |
| first_indexed | 2024-03-13T03:18:52Z |
| format | Article |
| id | doaj.art-24e94d5bac0b46369b31a3d982058e7b |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-13T03:18:52Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-24e94d5bac0b46369b31a3d982058e7b2023-06-25T11:24:57ZengNature PortfolioCommunications Biology2399-36422023-06-016111810.1038/s42003-023-05038-zA type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparumAmuza Byaruhanga Lucky0Chengqi Wang1Min Liu2Xiaoying Liang3Hui Min4Qi Fan5Faiza Amber Siddiqui6Swamy Rakesh Adapa7Xiaolian Li8Rays H. Y. Jiang9Xiaoguang Chen10Liwang Cui11Jun Miao12Department of Internal Medicine, Morsani College of Medicine, University of South FloridaCenter for Global Health and Infectious Diseases, Department of Global Health, University of South FloridaDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaDalian Institute of BiotechnologyDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaCenter for Global Health and Infectious Diseases, Department of Global Health, University of South FloridaDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaCenter for Global Health and Infectious Diseases, Department of Global Health, University of South FloridaDepartment of Pathogen Biology, School of Public Health, Southern Medical University, GuangzhouDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaAbstract Protein arginine methyltransferases (PRMTs) regulate many important cellular processes, such as transcription and RNA processing in model organisms but their functions in human malaria parasites are not elucidated. Here, we characterize PfPRMT5 in Plasmodium falciparum, which catalyzes symmetric dimethylation of histone H3 at R2 (H3R2me2s) and R8, and histone H4 at R3 in vitro. P fPRMT5 disruption results in asexual stage growth defects primarily due to lower invasion efficiency of the merozoites. Transcriptomic analysis reveals down-regulation of many transcripts related to invasion upon PfPRMT5 disruption, in agreement with H3R2me2s being an active chromatin mark. Genome-wide chromatin profiling detects extensive H3R2me2s marking of genes of different cellular processes, including invasion-related genes in wildtype parasites and PfPRMT5 disruption leads to the depletion of H3R2me2s. Interactome studies identify the association of PfPRMT5 with invasion-related transcriptional regulators such as AP2-I, BDP1, and GCN5. Furthermore, PfPRMT5 is associated with the RNA splicing machinery, and PfPRMT5 disruption caused substantial anomalies in RNA splicing events, including those for invasion-related genes. In summary, PfPRMT5 is critical for regulating parasite invasion and RNA splicing in this early-branching eukaryote.https://doi.org/10.1038/s42003-023-05038-z |
| spellingShingle | Amuza Byaruhanga Lucky Chengqi Wang Min Liu Xiaoying Liang Hui Min Qi Fan Faiza Amber Siddiqui Swamy Rakesh Adapa Xiaolian Li Rays H. Y. Jiang Xiaoguang Chen Liwang Cui Jun Miao A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum Communications Biology |
| title | A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum |
| title_full | A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum |
| title_fullStr | A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum |
| title_full_unstemmed | A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum |
| title_short | A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum |
| title_sort | type ii protein arginine methyltransferase regulates merozoite invasion in plasmodium falciparum |
| url | https://doi.org/10.1038/s42003-023-05038-z |
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