Efficiency of the pioneer round of translation affects the cellular site of nonsense-mediated mRNA decay.
Efficiency of the pioneer round of translation affects the cellular site of nonsense-mediated mRNA decay.
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DOI：
10.1016/j.molcel.2007.12.009
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发表时间：
2008-02
期刊：
影响因子：
16
通讯作者：
Hanae Sato;N. Hosoda;L. Maquat
中科院分区：
文献类型：
--
作者：
Hanae Sato;N. Hosoda;L. Maquat
在哺乳动物细胞中，无义介导的mRNA衰变（NMD）是先锋一轮翻译期间无义密码子识别的结果。这一轮可以在很大程度上发生在新合成的mRNA从细胞核释放之前或之后，这取决于mRNA，并且可能利用细胞质核糖体。我们表明，增加细胞浓度的剪接因子SF 2/ASF增强NMD的效率，并最终转移NMD后发生的mRNA出口到细胞质的NMD之前发生的mRNA从细胞核释放。这些变化伴随着先锋翻译起始复合物与SF 2/ASF、转录活性核糖体和翻译激活因子TAP的增加的关联。TAP结合的增加与SF 2/ASF结合的增加相关，但与REF/Aly或Y14结合的增加无关。我们的研究结果揭示了SF 2/ASF的额外作用，并表明先驱轮翻译的效率影响后续轮翻译的效率。
In mammalian cells, nonsense-mediated mRNA decay (NMD) is a consequence of nonsense codon recognition during a pioneer round of translation. This round can occur largely before or largely after the release of newly synthesized mRNA from nuclei, depending on the mRNA, and likely utilizes cytoplasmic ribosomes. We show that increasing the cellular concentration of the splicing factor SF2/ASF augments the efficiency of NMD and ultimately shifts NMD that takes place after mRNA export to the cytoplasm to NMD that occurs before mRNA release from nuclei. These changes are accompanied by an increased association of pioneer translation initiation complexes with SF2/ASF, translationally active ribosomes, and the translational activator TAP. Increased TAP binding correlates with increased SF2/ASF binding, but not increased REF/Aly or Y14 binding. Our results uncover an additional role for SF2/ASF and indicate that the efficiency of the pioneer round of translation influences the efficiency of subsequent rounds of translation.