Protein arginine methyltransferase 5 (PRMT5) is a major enzyme responsible for generating monomethyl and symmetric dimethyl arginine in proteins. PRMT5 is essential for cell viability and development, and its overexpression is observed in a variety of cancers. In the present study, it is found that levels of PRMT5 protein and symmetric arginine dimethylation in colorectal cancer (CRC) tissues are increased compared to those in adjacent noncancerous tissues. Using immunoaffinity enrichment of methylated peptides combined with high‐resolution mass spectrometry, a total of 147 symmetric dimethyl‐arginine (SDMA) sites in 94 proteins are identified, many of which are RNA binding proteins and enzymes. Quantitative analysis comparing CRC and normal tissues reveals significant increase in the symmetric dimethylation of 70 arginine sites in 46 proteins and a decrease in that of four arginine sites in four proteins. Among the 94 proteins identified in this study, it is confirmed that KH‐type splicing regulatory protein is a target of PRMT5 and highly expressed in CRC tissues compared to noncancerous tissues. This study is the first comprehensive analysis of symmetric arginine dimethylation using clinical samples and extends the number of known in vivo SDMA sites. The data obtained are available via ProteomeXchange with the identifier PXD015653.

中文翻译：

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使用免疫亲和富集和质谱法综合分析结直肠癌组织中的对称精氨酸二甲基化。


蛋白质精氨酸甲基转移酶 5 (PRMT5) 是负责在蛋白质中生成单甲基和对称二甲基精氨酸的主要酶。 PRMT5 对于细胞活力和发育至关重要，在多种癌症中观察到其过度表达。在本研究中，发现结直肠癌（CRC）组织中PRMT5蛋白和对称精氨酸二甲基化的水平比邻近非癌组织中的水平升高。利用甲基化肽的免疫亲和富集结合高分辨率质谱，在 94 个蛋白质中总共鉴定出了 147 个对称二甲基精氨酸 (SDMA) 位点，其中许多是 RNA 结合蛋白和酶。比较 CRC 和正常组织的定量分析显示，46 个蛋白质中 70 个精氨酸位点的对称二甲基化显着增加，而 4 个蛋白质中 4 个精氨酸位点的对称二甲基化显着减少。在本研究鉴定的 94 个蛋白中，证实 KH 型剪接调节蛋白是 PRMT5 的靶标，并且与非癌组织相比，在 CRC 组织中高表达。这项研究是首次使用临床样本对对称精氨酸二甲基化进行全面分析，并扩展了已知体内 SDMA 位点的数量。获得的数据可通过 ProteomeXchange 获得，标识符为 PXD015653。