In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome.
In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome.
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DOI：
10.1261/rna.079709.123
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发表时间：
2023-11
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U7 snRNP是一种多亚基核酸内切酶，参与后生动物复制依赖性组蛋白前体mRNA的3′端加工。与剪接体snRNP相反，U7 snRNP缺乏Sm亚基D1和D2，而是包含两个相关蛋白Lsm10和Lsm11。U7七聚体Sm环的其余五个亚基SmE、F、G、B和D3与剪接体snRNP共享。组装U7 snRNP独特环的途径尚不清楚。在这里，我们表明，Lsm10和Lsm11的异源二聚体与甲基化体，精氨酸甲基转移酶PRMT 5，MEP 50和pICln的复合物紧密相互作用，已知甲基化丝氨酸的羧基末端区域的Sm蛋白B，D1和D3在剪接体Sm环组装。生物化学和冷冻电镜结构研究表明，这种相互作用是由PRMT5介导的，PRMT5结合并甲基化Lsm11氨基末端区域的两个精氨酸残基。令人惊讶的是，PRMT5还甲基化SmE中的氨基末端精氨酸，SmE是在剪接体snRNP的生物发生期间不经历这种类型的修饰的亚基。一个有趣的可能性是Lsm11和SmE的独特甲基化模式在U7 snRNP的组装中起着至关重要的作用。
U7 snRNP is a multisubunit endonuclease required for 3′ end processing of metazoan replication-dependent histone pre-mRNAs. In contrast to the spliceosomal snRNPs, U7 snRNP lacks the Sm subunits D1 and D2 and instead contains two related proteins, Lsm10 and Lsm11. The remaining five subunits of the U7 heptameric Sm ring, SmE, F, G, B, and D3, are shared with the spliceosomal snRNPs. The pathway that assembles the unique ring of U7 snRNP is unknown. Here, we show that a heterodimer of Lsm10 and Lsm11 tightly interacts with the methylosome, a complex of the arginine methyltransferase PRMT5, MEP50, and pICln known to methylate arginines in the carboxy-terminal regions of the Sm proteins B, D1, and D3 during the spliceosomal Sm ring assembly. Both biochemical and cryo-EM structural studies demonstrate that the interaction is mediated by PRMT5, which binds and methylates two arginine residues in the amino-terminal region of Lsm11. Surprisingly, PRMT5 also methylates an amino-terminal arginine in SmE, a subunit that does not undergo this type of modification during the biogenesis of the spliceosomal snRNPs. An intriguing possibility is that the unique methylation pattern of Lsm11 and SmE plays a vital role in the assembly of the U7 snRNP.