Disassembly of Exon Junction Complexes by PYM
Disassembly of Exon Junction Complexes by PYM
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DOI：
10.1016/j.cell.2009.02.042
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发表时间：
2009-05-01
期刊：
影响因子：
64.5
通讯作者：
Hentze, Matthias W.
中科院分区：
文献类型：
--
作者：
Gehring, Niels H.;Lamprinaki, Styliani;Hentze, Matthias W.
外显子连接复合物（Exon junction complex，EJC）在剪接过程中沉积在mRNA上，作为基因内含子外显子结构的定位标志，并指导细胞质中的转录后过程。通过翻译的EJC去除和再循环不太清楚，并已归因于核糖体通过。这项工作确定了核糖体相关蛋白PYM作为EJC分解因子，并定义了其功能机制。尽管EJC组装中间体对PYM具有抗性，但完全组装的EJC通过PYM从剪接的mRNA中解离。这种分解涉及PYM与EJC蛋白MAGOH-Y14的结合。PYM在细胞中的过表达破坏了EJC与剪接mRNA的结合，并抑制了无义介导的mRNA衰变。在PYM耗尽的细胞中，EJC在剪接的mRNA上积累，并且EJC蛋白质再循环受损。因此，PYM是EJC分解因子，其在体外和活细胞中均起作用，并且拮抗重要的EJC功能。
Exon junction complexes (EJCs) are deposited onto mRNAs during splicing, serve as positional landmarks for the intron exon structure of genes, and direct posttranscriptional processes in the cytoplasm. EJC removal and recycling by translation are ill understood and have been attributed to ribosomal passage. This work identifies the ribosome-associated protein PYM as an EJC disassembly factor and defines its mechanism of function. Whereas EJC assembly intermediates are resistant to PYM, fully assembled EJCs are dissociated from spliced mRNAs by PYM. This disassembly involves PYM binding to the EJC proteins MAGOH-Y14. PYM overexpression in cells disrupts EJC association with spliced mRNA and inhibits nonsense-mediated mRNA decay. In cells depleted of PYM, EJCs accumulate on spliced mRNAs and EJC protein recycling is impaired. Hence, PYM is an EJC disassembly factor that acts both in vitro and in living cells, and that antagonizes important EJC functions.