Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes.
Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes.
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人类无义介导的 RNA 衰变通过核酸内切作用广泛启动，并以 snoRNA 宿主基因为目标。
DOI：
10.1101/gad.246538.114
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发表时间：
2014-11-15
影响因子：
10.5
通讯作者：
Jensen TH
中科院分区：
文献类型：
--
作者：
Lykke-Andersen S;Chen Y;Ardal BR;Lilje B;Waage J;Sandelin A;Jensen TH
具有提前终止密码子（PTC）的真核RNA通过无义介导的衰变（NMD）被消除。Lykke-Andersen等人发现，SMG 6催化的核酸内切酶解广泛地启动了人类无义RNA的降解，而去帽则在较小程度上被使用。在它们的内含子中存在snoRNA的大部分基因产生相当数量的NMD敏感性剪接变体，表明这些RNA仅仅是主要snoRNA产生过程的副产物。具有提前终止密码子（PTC）的真核RNA通过无义介导的衰变（NMD）被消除。虽然人无义RNA降解可以通过PTC附近的内切核酸裂解事件或通过脱帽来启动，但这些活性对内源性底物的单独贡献仍未得到解决。在这里，我们使用NMD底物及其5′-3′衰变中间体的同时转录组鉴定来确定SMG 6催化的核酸内切酶解广泛地启动人类无义RNA的降解，而去帽在较小程度上被使用。我们还表明，很大一部分的基因托管snoRNA在其内含子中产生相当数量的NMD敏感的剪接变体，表明这些RNA仅仅是一个主要的snoRNA生产过程的副产品。此外，来自编码多个snoRNA的基因的转录物通常产生允许单个共编码snoRNA的差异表达的替代转录物同种型。基于我们的研究结果，我们假设snoRNA宿主基因需要高度转录以适应高水平的snoRNA产生，并且单个snoRNA及其同源剪接RNA的表达可以通过选择性剪接和NMD解偶联。
Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). Lykke-Andersen et al. discover that SMG6-catalyzed endonucleolysis widely initiates the degradation of human nonsense RNAs, whereas decapping is used to a lesser extent. A large proportion of genes hosting snoRNAs in their introns produce considerable amounts of NMD-sensitive splice variants, indicating that these RNAs are merely by-products of a primary snoRNA production process. Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has remained unresolved. Here we used concurrent transcriptome-wide identification of NMD substrates and their 5′–3′ decay intermediates to establish that SMG6-catalyzed endonucleolysis widely initiates the degradation of human nonsense RNAs, whereas decapping is used to a lesser extent. We also show that a large proportion of genes hosting snoRNAs in their introns produce considerable amounts of NMD-sensitive splice variants, indicating that these RNAs are merely by-products of a primary snoRNA production process. Additionally, transcripts from genes encoding multiple snoRNAs often yield alternative transcript isoforms that allow for differential expression of individual coencoded snoRNAs. Based on our findings, we hypothesize that snoRNA host genes need to be highly transcribed to accommodate high levels of snoRNA production and that the expression of individual snoRNAs and their cognate spliced RNA can be uncoupled via alternative splicing and NMD.
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影响因子：
64.5
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通讯作者：
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