Woeller Collynn F, Gaspari Martina, Isken Olaf, Maquat Lynne E
Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 712, Rochester, New York 14642, USA.
EMBO Rep. 2008 May;9(5):446-51. doi: 10.1038/embor.2008.36. Epub 2008 Mar 28.
Nonsense-mediated messenger RNA decay (NMD) generally degrades mRNAs that prematurely terminate translation as a means of quality control. NMD in mammalian cells targets newly spliced mRNA that is bound by the cap-binding protein heterodimer CBP80/20 and one or more post-splicing exon junction complexes during a pioneer round of translation. NMD targets mRNA that initiates translation using the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES), therefore NMD might target not only CBP80/20-bound mRNA but also its remodelled product, eIF4E-bound mRNA. Here, we provide evidence that NMD triggered by translation initiation at the EMCV IRES, similar to NMD triggered by translation initiation at an mRNA cap, targets CBP80/20-bound mRNA but does not detectably target eIF4E-bound mRNA. We show that EMCV IRES-initiated translation undergoes a CBP80/20-associated pioneer round of translation that results in CBP80/20-dependent and Upf factor-dependent NMD when translation terminates prematurely.
无义介导的信使核糖核酸衰变（NMD）通常会降解过早终止翻译的信使核糖核酸（mRNA），作为一种质量控制手段。哺乳动物细胞中的NMD靶向新剪接的mRNA，这种mRNA在首次翻译过程中与帽结合蛋白异二聚体CBP80/20以及一个或多个剪接后外显子连接复合体结合。NMD靶向利用脑心肌炎病毒（EMCV）内部核糖体进入位点（IRES）起始翻译的mRNA，因此NMD可能不仅靶向与CBP80/20结合的mRNA，还靶向其重塑产物，即与真核起始因子4E（eIF4E）结合的mRNA。在此，我们提供证据表明，由EMCV IRES处的翻译起始引发的NMD，类似于由mRNA帽处的翻译起始引发的NMD，靶向与CBP80/20结合的mRNA，但未检测到靶向与eIF4E结合的mRNA。我们表明，EMCV IRES起始的翻译经历一轮与CBP80/20相关的首次翻译，当翻译过早终止时，这会导致依赖CBP80/20和Upf因子的NMD。
