A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum.
A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum.
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DOI：
10.1038/s42003-023-05038-z
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发表时间：
2023-06-22
影响因子：
5.9
通讯作者：
Miao, Jun
中科院分区：
文献类型：
--
作者：
Lucky, Amuza Byaruhanga;Wang, Chengqi;Liu, Min;Liang, Xiaoying;Min, Hui;Fan, Qi;Siddiqui, Faiza Amber;Adapa, Swamy Rakesh;Li, Xiaolian;Jiang, Rays H. Y.;Chen, Xiaoguang;Cui, Liwang;Miao, Jun
蛋白精氨酸甲基转移酶（PRMTs）在模式生物中调控许多重要的细胞过程，如转录和RNA加工，但其在人类疟疾寄生虫中的功能尚不清楚。在此，我们对恶性疟原虫中的PfPRMT5进行了表征，它在体外催化组蛋白H3 （H3R2me2s）和R8的对称二甲基化，以及组蛋白H4在R3的对称二甲基化。PfPRMT5的破坏导致无性期生长缺陷，主要是由于分裂子的入侵效率较低。转录组学分析显示，PfPRMT5破坏后，许多与入侵相关的转录本下调，这与H3R2me2s是一个活跃的染色质标记一致。全基因组染色质谱检测到不同细胞过程基因的广泛H3R2me2s标记，包括野生型寄生虫的入侵相关基因，PfPRMT5的破坏导致H3R2me2s的消耗。相互作用组研究发现PfPRMT5与侵袭相关的转录调节因子如AP2-I、BDP1和GCN5存在关联。此外，PfPRMT5与RNA剪接机制相关，PfPRMT5的破坏导致RNA剪接事件的大量异常，包括入侵相关基因的剪接事件。综上所述，PfPRMT5在这种早期分支真核生物中对调节寄生虫入侵和RNA剪接至关重要。PfPRMT5在体外对称二甲基化组蛋白H3和H4，在体内负责组蛋白H3R2 （H3R2me2s）的二甲基化，是调节恶性疟原虫寄生虫入侵和RNA剪接所必需的。
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. PfPRMT5 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. PfPRMT5, symmetrically dimethylating histones H3 and H4 in vitro, and responsible for dimethylation of histone H3 at R2 (H3R2me2s) in vivo, is necessary for the regulation of parasite invasion and RNA splicing in Plasmodium falciparum.
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影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
14.9
作者：
Deitsch, KW;Driskill, CL;Wellems, TE
通讯作者：
Wellems, TE
影响因子：
16.6
作者：
Alam MM;Solyakov L;Bottrill AR;Flueck C;Siddiqui FA;Singh S;Mistry S;Viskaduraki M;Lee K;Hopp CS;Chitnis CE;Doerig C;Moon RW;Green JL;Holder AA;Baker DA;Tobin AB
通讯作者：
Tobin AB
影响因子：
3.5
作者：
Di Lorenzo A;Bedford MT
通讯作者：
Bedford MT
影响因子：
3.9
作者：
Batugedara, Gayani;Lu, Xueqing M.;Le Roch, Karine G.
通讯作者：
Le Roch, Karine G.