Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation
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DOI：
10.1261/rna.12506
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发表时间：
2006-06-01
期刊：
影响因子：
4.5
通讯作者：
Gehring, Niels H.
中科院分区：
文献类型：
--
作者：
Kunz, Joachim B.;Neu-Yilik, Gabriele;Gehring, Niels H.
外显子连接复合物（EJC）的组分hUpf 3a和hUpf 3b具有双重功能：它们促进无义介导的mRNA衰变（NMD），并且它们还调节翻译效率。这两种功能是相互依赖还是相互独立尚不清楚。我们的特点是在λ N/boxB为基础的系留系统中的hUpf 3蛋白的功能。尽管hUpf 3b和hUpf 3a之间具有高度的序列相似性，但hUpf 3a诱导NMD和刺激翻译的活性远低于hUpf 3b。我们表明，诱导NMD的hUpf 3蛋白需要与Y14，Magoh，BTZ，和eIF 4AIII的相互作用。介导这种相互作用并在NMD功能中区分hUpf 3a和hUpf 3b的蛋白质区域位于C-末端结构域中，并且完全包含在Upf 3b而不是Upf 3a蛋白质中高度保守的小序列内。翻译的刺激独立于这种相互作用，并由hUpf 3蛋白的其他区域决定，表明在NMD或翻译中存在不同的hUpf 3蛋白下游途径。
The exon-junction complex (EJC) components hUpf3a and hUpf3b serve a dual function: They promote nonsense-mediated mRNA decay (NMD), and they also regulate translation efficiency. Whether these two functions are interdependent or independent of each other is unknown. We characterized the function of the hUpf3 proteins in a lambda N/boxB-based tethering system. Despite the high degree of sequence similarity between hUpf3b and hUpf3a, hUpf3a is much less active than hUpf3b to induce NMD and to stimulate translation. We show that induction of NMD by hUpf3 proteins requires interaction with Y14, Magoh, BTZ, and eIF4AIII. The protein region that mediates this interaction and discriminates between hUpf3a and hUpf3b in NMD function is located in the C-terminal domain and fully contained within a small sequence that is highly conserved in Upf3b but not Upf3a proteins. Stimulation of translation is independent of this interaction and is determined by other regions of the hUpf3 protein, indicating the presence of different downstream pathways of hUpf3 proteins either in NMD or in translation.