A nuclear translation-like factor elF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay
A nuclear translation-like factor elF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay
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DOI：
10.1073/pnas.0400933101
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发表时间：
2004-03-23
影响因子：
11.1
通讯作者：
Sonenberg, N
中科院分区：
文献类型：
--
作者：
Ferraiuolo, MA;Lee, CS;Sonenberg, N
在真核生物中，当存在提前终止密码子（PTC）时，一种被称为无义介导的mRNA降解（NMD）的监测机制会降解mRNA。NMD需要翻译来读取mRNA的读码框并检测PTC。在前体mRNA剪接过程中，外显子 - 外显子连接复合物（EJC）被招募到成熟mRNA上外显子连接点上游20 - 24个核苷酸的区域。在EJC上游存在PTC会引发NMD。真核起始因子4A（eIF4A）III是一种核蛋白，它分别与翻译起始因子eIF4G和eIF4B在物理上或功能上相互作用，并且与起始因子eIF4AI/II具有极高的同一性。在此我们表明，针对eIF4AIII而非eIF4AI/II的小干扰RNA（siRNA）会抑制NMD。此外，在剪接过程中，eIF4AIII而非eIF4AI会特异性地被招募到EJC。eIF4AIII在细胞核中的剪接过程中被加载到mRNA上，具有与翻译起始因子相关的特性，并且在NMD中起作用，这些观察结果增加了eIF4AIII在NMD过程中替代eIF4AI/II的可能性。
In eukaryotes, a surveillance mechanism known as nonsense-mediated decay (NMD) degrades the mRNA when a premature-termination codon (PTC) is present. NMD requires translation to read the frame of the mRNA and detect the PTC. During pre-mRNA splicing, the exon-exon junction complex (EJC) is recruited to a region 20-24 nt upstream of the exon junction on the mature mRNA. The presence of a PTC upstream from the EX elicits NMD. Eukaryotic initiation factor 4A (elF4A) III is a nuclear protein that interacts physically or functionally with translation initiation factors eIF4G and eIF4B, respectively, and shares strikingly high identity with the initiation factors eIF4AI/II. Here we show that siRNA against eIF4AIII, but not against eIF4AI/II, inhibits NMD. Moreover, eIF4AIII, but not eIF4AI, is specifically recruited to the EJC during splicing. The observations that eIF4AIII is loaded onto the mRNA during splicing in the nucleus, has properties related to a translation initiation factor, and functions in NMD raises the possibility that eIF4AIII substitutes for eIF4AI/II during NMD.