Key result
hUpf3a induces less NMD and translation than hUpf3b, requiring C-terminal domain interactions.
Why the study?
The interdependence of the dual functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation efficiency regulation was unknown.
The study demonstrates that hUpf3b is more active than hUpf3a in inducing NMD and stimulating translation, and that these two functions operate via independent downstream pathways.
hUpf3a shows markedly lower NMD and translation activity than hUpf3b; leaves open whether their functions are independent in disease-relevant mRNA regulation.
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.
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Kunz et al. (2006) studied this question. hUpf3 proteins in a lambdaN/boxB-based tethering system was evaluated on Nonsense-mediated mRNA decay (NMD) and translation efficiency. hUpf3a is much less active than hUpf3b in inducing NMD and stimulating translation, with NMD induction requiring interaction with Y14, Magoh, BTZ, and eIF4AIII via the C-terminal domain.
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