Kunz Joachim B, Neu-Yilik Gabriele, Hentze Matthias W, Kulozik Andreas E, Gehring Niels H
Department for Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany.
RNA. 2006 Jun;12(6):1015-22. doi: 10.1261/rna.12506. Epub 2006 Apr 6.
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 lambdaN/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.
外显子连接复合体（EJC）组分hUpf3a和hUpf3b具有双重功能：它们促进无义介导的mRNA降解（NMD），并且还调节翻译效率。这两种功能是相互依赖还是相互独立尚不清楚。我们在基于λN/boxB的拴系系统中表征了hUpf3蛋白的功能。尽管hUpf3b和hUpf3a之间的序列相似性很高，但hUpf3a在诱导NMD和刺激翻译方面的活性远低于hUpf3b。我们表明，hUpf3蛋白诱导NMD需要与Y14、Magoh、BTZ和eIF4AIII相互作用。介导这种相互作用并在NMD功能中区分hUpf3a和hUpf3b的蛋白质区域位于C末端结构域，并且完全包含在Upf3b中高度保守但Upf3a蛋白中不保守的一小段序列内。翻译的刺激独立于这种相互作用，并且由hUpf3蛋白的其他区域决定，这表明hUpf3蛋白在NMD或翻译中存在不同的下游途径。
