The GATA transcription factor ELT-2 modulates both the expression and methyltransferase activity of PRMT-1 in Caenorhabditis elegans
The GATA transcription factor ELT-2 modulates both the expression and methyltransferase activity of PRMT-1 in Caenorhabditis elegans
复制标题
GATA 转录因子 ELT-2 调节秀丽隐杆线虫 PRMT-1 的表达和甲基转移酶活性
DOI：
10.1093/jb/mvy012
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Fukamizu Akiyoshi
中科院分区：
文献类型：
--
作者：
Araoi Sho;Daitoku Hiroaki;Yokoyama Atsuko;Kako Koichiro;Hirota Keiko;Fukamizu Akiyoshi
蛋白质精氨酸甲基转移酶1（PRMT 1）催化细胞蛋白质的不对称精氨酸二甲基化，从而调节各种生物学过程，包括基因调控、RNA代谢、细胞信号传导和DNA修复。由于prmt-1无效突变体完全消除了C.在秀丽线虫中，PRMT-1被认为在确定不对称精氨酸二甲基化的水平中起关键作用。然而，调节PRMT-1活性的潜在机制在很大程度上仍然未知。在这里，我们探索的转录因子，诱导PRMT-1的表达，通过RNAi筛选使用transgenicC。elegan共享gfp上游的prmt-1启动子。在529个克隆中，我们鉴定了一个加塔转录因子lt-2作为Pprmt-1：：gfp表达的正调控因子，并显示lt-2 RNAi在mRNA和蛋白水平上降低了内源性PRMT-1的表达。然而，令人惊讶的是，当ELT-2沉默时精氨酸甲基化水平增加，这意味着红细胞样转录因子（ELT）-2也可能具有抑制PRMT-1的甲基转移酶活性的能力。支持这一想法，GST下拉和免疫共沉淀试验证明了ELT-2和PRMT-1之间的相互作用。此外，我们发现ELT-2以剂量依赖性方式干扰PRMT-1诱导的精氨酸甲基化。总的来说，我们的结果说明了PRMT-1的两种调控模式，这可能决定了C.优雅的。
Protein arginine methyltransferase 1 (PRMT1) catalyzes asymmetric arginine dimethylation of cellular proteins and thus modulates various biological processes, including gene regulation, RNA metabolism, cell signaling and DNA repair. Sinceprmt-1null mutant completely abolishes asymmetric dimethylarginine inC. elegans, PRMT-1 is thought to play a crucial role in determining levels of asymmetric arginine dimethylation. However, the mechanism underlying the regulation of PRMT-1 activity remains largely unknown. Here, we explored for transcription factors that induce the expression of PRMT-1 by an RNAi screen using transgenicC. elegansharbouringprmt-1promoter upstream ofgfp. Of 529 clones, we identify a GATA transcription factorelt-2as a positive regulator ofPprmt-1:: gfpexpression and show thatelt-2RNAi decreases endogenous PRMT-1 expression at mRNA and protein levels. Nevertheless, surprisingly arginine methylation levels are increased whenelt-2is silenced, implying that erythroid-like transcription factor (ELT)-2 may also have ability to inhibit methyltransferase activity of PRMT-1. Supporting this idea, GST pull-down and co-immunoprecipitation assays demonstrate the interaction between ELT-2 and PRMT-1. Furthermore, we find that ELT-2 interferes with PRMT-1-induced arginine methylation in a dose-dependent manner. Collectively, our results illustrate the two modes of PRMT-1 regulation, which could determine the levels of asymmetric arginine dimethylation inC. elegans.