Arginine methylation mediated by the Arabidopsis homolog of PRMT5 is essential for proper pre-mRNA splicing
Arginine methylation mediated by the Arabidopsis homolog of PRMT5 is essential for proper pre-mRNA splicing
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PRMT5 的拟南芥同源物介导的精氨酸甲基化对于正确的前 mRNA 剪接至关重要
DOI：
10.1073/pnas.1009669107
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发表时间：
2010-11-02
影响因子：
11.1
通讯作者：
Cao, Xiaofeng
中科院分区：
文献类型：
--
作者：
Deng, Xian;Gu, Lianfeng;Cao, Xiaofeng
蛋白质精氨酸甲基化是最丰富、最重要的翻译后修饰之一，参与真核生物的多种生物过程，例如转录调控和 RNA 加工。对称精氨酸二甲基化是 snRNP 生物合成所必需的，并且被认为是前 mRNA 剪接所必需的；然而，除了体外证据外，它是否影响体内剪接仍然难以捉摸。拟南芥对称精氨酸二甲基转移酶 AtPRMT5 的突变会导致多效性发育缺陷，包括晚花，但其潜在的分子机制在很大程度上尚不清楚。在这里，我们表明 AtPRMT5 甲基化多种底物，包括一些 RNA 结合或加工因子以及参与 RNA 代谢的 U snRNP AtSmD1、D3 和 AtLSm4 蛋白。 RNA-seq 分析表明，AtPRMT5 缺陷会导致参与多种生物过程的数百个基因出现剪接缺陷。在一些参与调节开花时间的RNA加工因子的转录本中发现了剪接缺陷。特别是，atprmt5突变体中开花调节因子FLOWERING LOCUS KH DOMAIN (FLK)的剪接缺陷降低了其功能转录物和蛋白质水平，导致开花抑制因子FLOWERING LOCUS C (FLC)上调，从而导致开花延迟。总而言之，我们的研究结果揭示了精氨酸甲基化在影响不同发育过程的正确前 mRNA 剪接中的重要作用。
Protein arginine methylation, one of the most abundant and important posttranslational modifications, is involved in a multitude of biological processes in eukaryotes, such as transcriptional regulation and RNA processing. Symmetric arginine dimethylation is required for snRNP biogenesis and is assumed to be essential for pre-mRNA splicing; however, except for in vitro evidence, whether it affects splicing in vivo remains elusive. Mutation in an Arabidopsis symmetric arginine dimethyltransferase, AtPRMT5, causes pleiotropic developmental defects, including late flowering, but the underlying molecular mechanism is largely unknown. Here we show that AtPRMT5 methylates a wide spectrum of substrates, including some RNA binding or processing factors and U snRNP AtSmD1, D3, and AtLSm4 proteins, which are involved in RNA metabolism. RNA-seq analyses reveal that AtPRMT5 deficiency causes splicing defects in hundreds of genes involved in multiple biological processes. The splicing defects are identified in transcripts of several RNA processing factors involved in regulating flowering time. In particular, splicing defects at the flowering regulator FLOWERING LOCUS KH DOMAIN (FLK) in atprmt5 mutants reduce its functional transcript and protein levels, resulting in the up-regulation of a flowering repressor FLOWERING LOCUS C (FLC) and consequently late flowering. Taken together, our findings uncover an essential role for arginine methylation in proper pre-mRNA splicing that impacts diverse developmental processes.