NONU-1 Encodes a Conserved Endonuclease Required for mRNA Translation Surveillance
NONU-1 Encodes a Conserved Endonuclease Required for mRNA Translation Surveillance
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DOI：
10.1016/j.celrep.2020.03.023
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发表时间：
2020-03-31
期刊：
影响因子：
8.8
通讯作者：
Arribere, Joshua A.
中科院分区：
文献类型：
--
作者：
Glover, Marissa L.;Burroughs, A. Max;Arribere, Joshua A.
细胞翻译监视拯救了在有问题的mRNA上停滞的核糖体。在翻译监视期间，有问题的mRNA的核酸内切裂解是拯救停滞的核糖体的关键步骤。在这里，我们确定NONU-1作为翻译监视途径所需的一个因子，包括不去和不停止的mRNA衰减。我们发现：（1）NONU-1降低了nonstop和no-go mRNA水平;（2）NONU-1含有mRNA衰变所需的Smr RNA酶结构域;（3）NONU-1的结构域结构和催化残基分别在后生动物和真核生物中保守;（4）NONU-1是在停滞核糖体附近形成mRNA切割片段所必需的。我们将结果推广到C. elegans与S.酿酒酵母，显示NONU-1的进化保守功能。我们的工作确定了一个对翻译监测至关重要的因素，并将为翻译和mRNA衰变交叉点的机制研究提供信息。
Cellular translation surveillance rescues ribosomes that stall on problematic mRNAs. During translation surveillance, endonucleolytic cleavage of the problematic mRNA is a critical step in rescuing stalled ribosomes. Here we identify NONU-1 as a factor required for translation surveillance pathways including no-go and nonstop mRNA decay. We show that (1) NONU-1 reduces nonstop and no-go mRNA levels; (2) NONU-1 contains an Smr RNase domain required for mRNA decay; (3) the domain architecture and catalytic residues of NONU-1 are conserved throughout metazoans and eukaryotes, respectively; and (4) NONU-1 is required for the formation of mRNA cleavage fragments in the vicinity of stalled ribosomes. We extend our results in C. elegans to homologous factors in S. cerevisiae, showing the evolutionarily conserved function of NONU-1. Our work establishes the identity of a factor critical to translation surveillance and will inform mechanistic studies at the intersection of translation and mRNA decay.