Premature Termination Codons Are Recognized in the Nucleus in A Reading-Frame Dependent Manner.
Premature Termination Codons Are Recognized in the Nucleus in A Reading-Frame Dependent Manner.
复制标题
过早终止密码子在细胞核中以依赖于阅读框架的方式被识别
DOI：
10.1038/celldisc.2015.1
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发表时间：
2015
期刊：
影响因子：
33.5
通讯作者：
Cheng H
中科院分区：
文献类型：
--
作者：
Shi M;Zhang H;Wang L;Zhu C;Sheng K;Du Y;Wang K;Dias A;Chen S;Whitman M;Wang E;Reed R;Cheng H
已知含有提前终止密码子（PTC）的mRNA通过无义介导的mRNA衰变（NMD）降解。出乎意料的是，我们发现含有任何类型的PTC（UAA，UAG和UGA）的mRNA被滞留在细胞核中，而它们的野生型对应物则被迅速输出。这种保留严格依赖于阅读框架。引人注目的是，我们的数据表明，核中的翻译核糖体校对框架并检测核中的PTC。此外，穿梭NMD蛋白Upf 1特异性地与细胞核中的PTC+ mRNA（含PTC的mRNA）结合，并且是PTC+ mRNA的细胞核保留所需的。总之，我们的数据导致了一个工作模型，即PTC通过翻译核糖体在细胞核中被识别，导致Upf 1的募集，Upf 1反过来又在PTC+mRNA的核保留中发挥作用。核PTC识别为mRNA增加了一个新的校对层，对于确保蛋白质生产所需的非凡保真度可能至关重要。
mRNAs containing premature termination codons (PTCs) are known to be degraded via nonsense-mediated mRNA decay (NMD). Unexpectedly, we found that mRNAs containing any type of PTCs (UAA, UAG, and UGA) are detained in the nucleus, whereas their wild-type counterparts are rapidly exported. This retention is strictly reading-frame dependent. Strikingly, our data indicate that translating ribosomes in the nucleus proofread the frame and detect the PTCs in the nucleus. Moreover, the shuttling NMD protein Upf1 specifically associates with PTC+mRNAs (PTC-containing mRNAs) in the nucleus and is required for nuclear retention of PTC+mRNAs. Together, our data lead to a working model that PTCs are recognized in the nucleus by translating ribosomes, resulting in recruitment of Upf1, which in turn functions in nuclear retention of PTC+mRNA. Nuclear PTC recognition adds a new layer of proofreading for mRNA and may be vital for ensuring the extraordinary fidelity required for protein production.