3′ UTR Length and Messenger Ribonucleoprotein Composition Determine Endocleavage Efficiencies at Termination Codons
3′ UTR Length and Messenger Ribonucleoprotein Composition Determine Endocleavage Efficiencies at Termination Codons
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DOI：
10.1016/j.celrep.2014.09.012
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发表时间：
2014-10-23
期刊：
影响因子：
8.8
通讯作者：
Gehring, Niels H.
中科院分区：
文献类型：
--
作者：
Boehm, Volker;Haberman, Nejc;Gehring, Niels H.
无义介导的mRNA衰变（NMD）降解不同类型的mRNA，包括带有过早终止密码子（ptc）的转录本。NMD因子SMG6通过核内裂解启动底物mrna的降解。在这里，我们的目标是描述nmd激活事件的级联，最终导致内切。我们报道，长3' utr引发smg6介导的核内溶解降解。3' UTR内外显子结复合体（EJC）的存在以一种与距离无关的方式强烈刺激内切。内切不需要SMG6与EJCs的相互作用。虽然核心NMD成分UPF2支持长3' UTR mrna的核内分解衰变，但在ejc刺激的内切过程中，它大多是必不可少的。利用高通量测序，我们将不同的ptc -含报告mrna和内源性NMD底物的内切位置映射到终止密码子的直接和下游区域。这些结果揭示了信使核糖核蛋白（mRNP）参数如何差异地影响smg6执行的核内溶解，并揭示了与翻译终止相关的这种现象的核心特征。
Nonsense-mediated mRNA decay (NMD) degrades different classes of mRNAs, including transcripts with premature termination codons (PTCs). The NMD factor SMG6 initiates degradation of substrate mRNAs by endonucleolytic cleavage. Here, we aim to delineate the cascade of NMD-activating events that culminate in endocleavage. We report that long 3' UTRs elicit SMG6-mediated endonucleolytic degradation. The presence of an exon-junction complex (EJC) within the 3' UTR strongly stimulates endocleavage in a distance-independent manner. The interaction of SMG6 with EJCs is not required for endocleavage. Whereas the core NMD component UPF2 supports endonucleolytic decay of long 3' UTR mRNAs, it is mostly dispensable during EJC-stimulated endocleavage. Using high-throughput sequencing, we map endocleavage positions of different PTC-containing reporter mRNAs and an endogenous NMD substrate to regions directly at and downstream of the termination codon. These results reveal how messenger ribonucleoprotein (mRNP) parameters differentially influence SMG6-executed endonucleolysis and uncover central characteristics of this phenomenon associated with translation termination.