TLS and PRMT1 synergistically coactivate transcription at the survivin promoter through TLS arginine methylation
TLS and PRMT1 synergistically coactivate transcription at the survivin promoter through TLS arginine methylation
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DOI：
10.1016/j.bbrc.2010.12.097
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发表时间：
2011-01-28
影响因子：
3.1
通讯作者：
Kurokawa, Riki
中科院分区：
文献类型：
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作者：
Du, Kun;Arai, Shigeki;Kurokawa, Riki
TLS（脂肪肉瘤易位）也称为 FUS，是一种多功能蛋白，与多种细胞事件有关，例如维持基因组完整性和调节基因表达。我们重点关注 TLS 作为转录调控核心调控因子的作用。在研究TLS结合蛋白的过程中，我们发现PRMT1（蛋白精氨酸甲基转移酶1）与TLS形成复合物。我们分析了内源 TLS 的甲基化状态，并证明 TLS 被 PRMT1 精氨酸甲基化。通过质谱分析，我们发现 TLS 中的四个精氨酸残基（R216、R218、R242 和 R394）一致被二甲基化。我们进行了荧光素酶报告基因检测，以评估 TLS 精氨酸甲基化在转录调控中的功能后果，有趣的是，我们观察到 TLS 和 PRMT1 协同共激活存活蛋白启动子处的转录。使用催化死亡 PRMT1 或甲基化抑制剂的进一步分析均表明协同转录激活是由 TLS 精氨酸甲基化介导的。这些结果揭示了 TLS 和 PRMT1 在转录调控中的协同作用。 (C) 2010 Elsevier Inc. 保留所有权利。
TLS (Translocated in LipoSarcoma), also termed FUS, is a multifunctional protein implicated in diverse cellular events such as maintaining genome integrity and regulating gene expression. We have focused on the role of TLS as a coregulator in transcriptional regulation. In the process of investigating TLS-binding proteins, we found that PRMT1 (protein arginine methyltransferase 1) was in complex with TLS. We analyzed the methylation status of endogenous TLS and demonstrated that TLS was arginine-methylated by PRMT1. Using mass spectrometry, we identified that four arginine residues within TLS (R216, R218, R242 and R394) were consistently dimethylated. We performed luciferase reporter assays to assess the functional consequence of TLS arginine methylation in transcriptional regulation and, interestingly, observed that TLS and PRMT1 synergistically coactivated transcription at the survivin promoter. Further analysis using a catalytic-dead PRMT1 or methylation inhibitor both showed that the synergistic transcriptional activation was mediated by TLS arginine-methylation. These results revealed a cooperative role of TLS and PRMT1 in transcriptional regulation. (C) 2010 Elsevier Inc. All rights reserved.