Protein Arginine Methylation Facilitates Cotranscriptional Recruitment of Pre-mRNA Splicing Factors
Protein Arginine Methylation Facilitates Cotranscriptional Recruitment of Pre-mRNA Splicing Factors
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DOI：
10.1128/mcb.00359-10
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发表时间：
2010-11-01
影响因子：
5.3
通讯作者：
Yu, Michael C.
中科院分区：
文献类型：
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作者：
Chen, Yin-Chu;Milliman, Eric J.;Yu, Michael C.
共转录将前 mRNA 剪接因子招募到其基因组靶标中，有助于成熟信使核糖核蛋白颗粒 (mRNP) 的高效有序组装。然而，剪接因子的共转录招募是如何调节的仍然很大程度上未知。在这里，我们证明蛋白质精氨酸甲基化在酿酒酵母中调节这一过程中发挥着新的作用。我们的数据显示，Hmt1（主要的 I 型精氨酸甲基转移酶）可甲基化 Snp1（一种 U1 小核 RNP (snRNP) 特异性蛋白），并且哺乳动物 Snp1 同源物 U1-70K 也同样被甲基化。全基因组定位分析表明，HMT1 基因的删除会解除对 U1 snRNP 及其相关成分向含内含子基因 (ICG) 的招募的调节。在相同的背景下，作用于 U1 snRNP 添加下游的剪接因子与 ICG 的数量减少。剪接目标转录物丰度的定量测量表明，募集的这些变化导致发育调控 mRNA 的剪接效率增加。我们还表明，在 Hmt1 或其催化活性缺失的情况下，Snp1 和 SR 样蛋白 Npl3 之间的关联显着增加。总之，这些数据支持了一个模型，即精氨酸甲基化调节 SR 样蛋白和前 mRNA 剪接因子之间的动态关联，以促进剪接中的靶标特异性。
Cotranscriptional recruitment of pre-mRNA splicing factors to their genomic targets facilitates efficient and ordered assembly of a mature messenger ribonucleoprotein particle (mRNP). However, how the cotranscriptional recruitment of splicing factors is regulated remains largely unknown. Here, we demonstrate that protein arginine methylation plays a novel role in regulating this process in Saccharomyces cerevisiae. Our data show that Hmt1, the major type I arginine methyltransferase, methylates Snp1, a U1 small nuclear RNP (snRNP)-specific protein, and that the mammalian Snp1 homolog, U1-70K, is likewise arginine methylated. Genome-wide localization analysis reveals that the deletion of the HMT1 gene deregulates the recruitment of U1 snRNP and its associated components to intron-containing genes (ICGs). In the same context, splicing factors acting downstream of U1 snRNP addition bind to a reduced number of ICGs. Quantitative measurement of the abundance of spliced target transcripts shows that these changes in recruitment result in an increase in the splicing efficiency of developmentally regulated mRNAs. We also show that in the absence of either Hmt1 or of its catalytic activity, an association between Snp1 and the SR-like protein Npl3 is substantially increased. Together, these data support a model whereby arginine methylation modulates dynamic associations between SR-like protein and pre-mRNA splicing factor to promote target specificity in splicing.