文章：

蛋白质精氨酸甲基转移酶与癌症

Protein arginine methyltransferases and cancer

原文发布日期：2012-12-13

DOI: 10.1038/nrc3409

类型: Review Article

开放获取: 否

要点：

1. Nine protein arginine methyltransferases (PRMTs) are encoded in mammalian genomes. Each PRMT isoform harbours the characteristic motifs of the seven-β-strand methyltransferase family, as well as additional 'double E' and 'THW' sequence motifs that are particular to the PRMT subfamily of methyltransferases.
2. The PRMTs catalyse three types of arginine methylation. Monomethylation is regarded as an intermediate in the formation of dimethylated arginine. PRMT1 is the primary enzyme responsible for asymmetric dimethylation, and PRMT5 is the primary enzyme responsible for symmetric dimethylation.
3. Prmt1- and Prmt5-knockout mice die very early during development, probably when the maternal RNA pool is depleted. This reflects the housekeeping nature of the two enzymes encoded by these genes. Co-activator-associated arginine methyltransferase 1 (Carm1)-knockout mice die at birth and display differentiational defects in a number of cell types. Knockout mice missing Prmt2, Prmt3 and Prmt6 are viable.
4. The expression of some genes encoding PRMTs may be altered in certain cancers. The nuclear receptor co-activators PRMT1 and CARM1 are overexpressed in breast cancers and prostate cancers. The transcriptional co-repressors PRMT5 and PRMT6 suppress the expression of tumour suppressor genes and are overexpressed in lung cancer and blood cancers.
5. Proteins that harbour tudor domains bind selectively to arginine-methylated motifs. The overexpression of methylarginine effector molecules, such as tudor domain-containing protein 3 (TDRD3), is linked to poor prognosis for the survival of patients with breast cancer.
6. Whole-genome analyses of cancers have revealed cancer-associated alterations in PRMT8, but in no other PRMT. It is likely that cancer-associated mutations might be identified in additional PRMTs as sequencing depth increases and additional cancer types are explored.

要点翻译：

1. 哺乳动物基因组中编码有九种蛋白质精氨酸甲基转移酶（PRMT）。每种PRMT亚型均包含七β链甲基转移酶家族的特征性模体，以及甲基转移酶中PRMT亚族特有的额外“双E”和“THW”序列模体。
2. PRMTs催化三种类型的精氨酸甲基化。单甲基化被认为是形成二甲基化精氨酸的中间步骤。PRMT1是负责不对称二甲基化的主要酶，而PRMT5是负责对称二甲基化的主要酶。
3. Prmt1和Prmt5基因敲除小鼠在发育早期（可能是在母体RNA库耗竭时）死亡，这反映了这两个基因所编码酶的看家特性。共激活因子相关精氨酸甲基转移酶1（Carm1）基因敲除小鼠在出生时死亡，并在多种细胞类型中表现出分化缺陷。缺失Prmt2、Prmt3和Prmt6的基因敲除小鼠能够存活。
4. 在某些癌症中，编码PRMTs的某些基因表达可能发生改变。核受体共激活因子PRMT1和CARM1在乳腺癌和前列腺癌中过度表达。转录共抑制因子PRMT5和PRMT6可抑制肿瘤抑制基因的表达，并在肺癌和血癌中过度表达。
5. 携带tudor结构域的蛋白质选择性结合精氨酸甲基化模体。甲基精氨酸效应分子（如含有tudor结构域的蛋白3（TDRD3））的过度表达与乳腺癌患者的不良预后相关。
6. 癌症的全基因组分析揭示了PRMT8中存在癌症相关改变，但在其他PRMT中未发现。随着测序深度的增加和更多癌症类型的探索，很可能在其他PRMT中发现与癌症相关的突变。

英文摘要：

There are nine protein arginine methyltransferases (PRMTs) encoded in mammalian genomes, the protein products of which catalyse three types of arginine methylation — monomethylation and two types of dimethylation. Protein arginine methylation is an abundant modification that has been implicated in signal transduction, gene transcription, DNA repair and mRNA splicing, among others. Studies have only recently linked this modification to carcinogenesis and metastasis. Sequencing studies have not generally found alterations to the PRMTs; however, overexpression of these enzymes is often associated with various cancers, which might make some of them viable targets for therapeutic strategies.

摘要翻译： 

哺乳动物基因组编码有九种蛋白质精氨酸甲基转移酶（PRMTs），其蛋白产物催化三种类型的精氨酸甲基化——单甲基化和两种类型的二甲基化。蛋白质精氨酸甲基化是一种丰富的修饰，与信号转导、基因转录、DNA修复和mRNA剪接等多种过程有关。直到最近，研究才将这种修饰与癌症发生和转移联系起来。测序研究通常未发现PRMTs的变异；然而，这些酶的过表达常与多种癌症相关，这可能使它们成为治疗策略的可行靶点。

原文链接：

Protein arginine methyltransferases and cancer