Structure of the 80S ribosome–Xrn1 nuclease complex

Structure of the 80S ribosome–Xrn1 nuclease complex
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80S 核糖体âXrn1 核酸酶复合物的结构

DOI:
10.1038/s41594-019-0202-5
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发表时间:
2019
影响因子:
16.8
通讯作者:
Beckmann
Beckmann
中科院分区:
生物学1区
文献类型:
--
作者:
Tesina;Heckel;Fromont-Racine;Buschauer;Beatrix;Berninghausen;Jacquier;Becker;Beckmann

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信使RNA(信使RNA)动态平衡是基因表达的重要组成部分,其中RNA聚合酶产生的信使RNA被核酸酶的降解所抵消。保守的5‘-to-3’外切核糖核酸酶Xrn1通过在翻译后降解去连接或裂解的mRNAs,以及更令人惊讶的是,也在共翻译过程中,在真核细胞的mRNA动态平衡中起着至关重要的作用。在这里,我们报道了Active Xrn1可以直接和特异性地与翻译机器相互作用。程序化的酿酒酵母80S核糖体-Xrn1核糖酶复合体的冷冻电子显微镜结构揭示了Xrn1的保守核心是如何与核糖体的mRNA出口结合的。这个界面提供了一条管道,将核糖体解码位点的基因直接导入核酸酶的活性中心,从而将基因的解码与降解分离了17 ± 1核苷酸。这些发现解释了5‘到3’信使核糖核酸的快速降解如何有效地与其最后一轮信使核糖核酸的翻译相结合。
Messenger RNA (mRNA) homeostasis represents an essential part of gene expression, in which the generation of mRNA by RNA polymerase is counter-balanced by its degradation by nucleases. The conserved 5′-to-3′ exoribonuclease Xrn1 has a crucial role in eukaryotic mRNA homeostasis by degrading decapped or cleaved mRNAs post-translationally and, more surprisingly, also co-translationally. Here we report that active Xrn1 can directly and specifically interact with the translation machinery. A cryo-electron microscopy structure of a programmedSaccharomyces cerevisiae80S ribosome–Xrn1 nuclease complex reveals how the conserved core of Xrn1 enables binding at the mRNA exit site of the ribosome. This interface provides a conduit for channelling of the mRNA from the ribosomal decoding site directly into the active center of the nuclease, thus separating mRNA decoding from degradation by only 17 ± 1 nucleotides. These findings explain how rapid 5′-to-3′ mRNA degradation is coupled efficiently to its final round of mRNA translation.
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