Nuclear export of hnRNP Hrp1p and nuclear export of hnRNP Npl3p are linked and influenced by the methylation state of Npl3p.
Nuclear export of hnRNP Hrp1p and nuclear export of hnRNP Npl3p are linked and influenced by the methylation state of Npl3p.
复制标题
hnRNP Hrp1p 的核输出和 hnRNP Npl3p 的核输出相互关联并受 Npl3p 甲基化状态的影响。
DOI：
10.1128/mcb.24.24.10742-10756.2004
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发表时间：
2004
影响因子：
5.3
通讯作者：
Henry,MichaelF
中科院分区：
文献类型：
--
作者：
Xu,Chong;Henry,MichaelF
真核生物 mRNA 的加工和输出是由一系列由异质核核糖核蛋白 (hnRNP) 组成的复合物介导的。许多 hnRNP 在其 RGG 结构域内的精氨酸残基处被甲基化。尽管细胞精氨酸甲基化对于几种 hnRNP 的有效核输出是必需的，但其在此过程中的作用尚不清楚。为了解决这个问题，我们用 KGG 替换了两个 hnRNP（Npl3p 和 Hrp1p）的甲基化 RGG 三肽。我们发现这些取代专门消除了它们的甲基化，但对它们的核输出活性有不同的影响。虽然Hrp1p的有效输出需要细胞甲基转移酶活性，但Hrp1p本身的修饰是可有可无的。相比之下，我们发现Npl3精氨酸甲基化不仅促进其自身的输出，而且也是Hrp1p有效离开细胞核所必需的。与这一观察结果一致，我们发现 Npl3p 和 Hrp1p 存在于核糖核蛋白复合物中。我们提供了第一个证据表明特定蛋白质的精氨酸甲基化直接影响其活性。有效的输出本身不需要甲基化，但未甲基化的精氨酸残基会导致 hnRNP 的保留。因此，精氨酸甲基化用于掩盖 Npl3p RGG 结构域，以实现有效的核糖核蛋白输出。
Eukaryotic mRNA processing and export are mediated by a series of complexes composed of heterogeneous nuclear ribonucleoproteins (hnRNPs). Many of these hnRNPs are methylated at arginine residues within their RGG domains. Although cellular arginine methylation is required for the efficient nuclear export of several hnRNPs, its role in this process is unknown. To address this question, we replaced the methylated RGG tripeptides of two hnRNPs, Npl3p and Hrp1p, with KGG. We found that these substitutions specifically abolish their methylation but have different effects on their nuclear export activity. Although the efficient export of Hrp1p requires cellular methyltransferase activity, the modification of Hrp1p itself is dispensable. In contrast, we found that Npl3 arginine methylation not only facilitates its own export but also is required for Hrp1p to efficiently exit the nucleus. Consistent with this observation, we found that Npl3p and Hrp1p exist in a ribonucleoprotein complex. We provide the first evidence that the arginine methylation of a particular protein directly affects its activity. Efficient export does not require methylation per se, but unmethylated arginine residues lead to retention of hnRNPs. Thus, arginine methylation serves to mask the Npl3p RGG domain for efficient ribonucleoprotein export.