Alternative splicing yields protein arginine methyltransferase 1 isoforms with distinct activity, substrate specificity, and subcellular localization
Alternative splicing yields protein arginine methyltransferase 1 isoforms with distinct activity, substrate specificity, and subcellular localization
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DOI：
10.1074/jbc.m704349200
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发表时间：
2007-11-09
影响因子：
4.8
通讯作者：
Cote, Jocelyn
中科院分区：
文献类型：
--
作者：
Goulet, Isabelle;Gauvin, Gabrielle;Cote, Jocelyn
PRMT 1是蛋白质精氨酸甲基转移酶（PRMTs）家族的主要成员，其已经涉及各种细胞过程，包括转录、RNA加工和信号转导。先前报道，人PRMT 1前mRNA被选择性剪接以产生具有不同N-末端序列的三种同种型。对PRMT 1基因5 '端的基因组组织的仔细检查显示，它可以产生多达7种蛋白质同种型，所有这些蛋白质同种型在其N-末端结构域中都是不同的。这些变体的详细生物化学表征显示，独特的N-末端序列可以影响催化活性以及底物特异性。此外，我们的研究结果揭示了PRMT 1v 2中存在功能性核输出序列。最后，我们发现PRMT 1亚型的相对平衡在乳腺癌中被改变。
PRMT1 is the predominant member of a family of protein arginine methyltransferases (PRMTs) that have been implicated in various cellular processes, including transcription, RNA processing, and signal transduction. It was previously reported that the human PRMT1 pre-mRNA was alternatively spliced to yield three isoforms with distinct N-terminal sequences. Close inspection of the genomic organization in the 5'-end of the PRMT1 gene revealed that it can produce up to seven protein isoforms, all varying in their N-terminal domain. A detailed biochemical characterization of these variants revealed that unique N-terminal sequences can influence catalytic activity as well as substrate specificity. In addition, our results uncovered the presence of a functional nuclear export sequence in PRMT1v2. Finally, we find that the relative balance of PRMT1 isoforms is altered in breast cancer.