Liu Q, Dreyfuss G
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148, USA.
Mol Cell Biol. 1995 May;15(5):2800-8. doi: 10.1128/MCB.15.5.2800.
Heterogenous nuclear ribonucleoproteins (hnRNPs) bind pre-mRNAs and facilitate their processing into mRNAs. Many of the hnRNPs undergo extensive posttranslational modifications including methylation on arginine residues. hnRNPs contain about 65% of the total NG,NG-dimethylarginine found in the cell nucleus. The role of this modification is not known. Here we identify the hnRNPs that are methylated in HeLa cells and demonstrate that most of the pre-mRNA-binding proteins receive this modification. Using recombinant human hnRNP A1 as a substrate, we have partially purified and characterized a protein-arginine N-methyltransferase specific for hnRNPs from HeLa cells. This methyltransferase can methylate the same subset of hnRNPs in vitro as are methylated in vivo. Furthermore, it can also methylate other RNA-binding proteins that contain the RGG motif RNA-binding domain. This activity is evolutionarily conserved from lower eukaryotes to mammals, suggesting that methylation has a significant role in the function of RNA-binding proteins.
不均一核核糖核蛋白（hnRNPs）与前体mRNA结合，并促进其加工成mRNA。许多hnRNPs经历广泛的翻译后修饰，包括精氨酸残基的甲基化。hnRNPs含有细胞核中发现的总NG，NG-二甲基精氨酸的约65％。这种修饰的作用尚不清楚。在这里，我们鉴定了在HeLa细胞中甲基化的hnRNPs，并证明大多数前体mRNA结合蛋白都接受这种修饰。使用重组人hnRNP A1作为底物，我们部分纯化并鉴定了一种对HeLa细胞中hnRNPs特异的蛋白质精氨酸N-甲基转移酶。这种甲基转移酶在体外可以甲基化与体内甲基化相同的hnRNPs亚组。此外，它还可以甲基化其他含有RGG基序RNA结合结构域的RNA结合蛋白。这种活性从低等真核生物到哺乳动物在进化上是保守的，表明甲基化在RNA结合蛋白的功能中具有重要作用。
