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 PTC (UAA, UAG, 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+ mRNA in the nucleus and is required for nuclear retention of PTC+ mRNA. 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.

中文翻译：

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早熟终止密码子在核中以阅读框架依赖性方式被识别。

已知包含过早终止密码子（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PTC（UAA，UAG，UGA）的mRNA被保留在细胞核中，而它们的野生型对应物却迅速输出。此保留严格取决于阅读框架。令人惊讶的是，我们的数据表明核中的翻译核糖体对框架进行了校对并检测了核中的PTC。此外，穿梭的NMD蛋白Upf1与细胞核中的PTC + mRNA特异性结合，并且是PTC + mRNA的核保留所必需的。在一起，我们的数据导致一个工作模型，即通过翻译核糖体在核中识别PTC，从而募集Upf1，这反过来又在PTC + mRNA的核保留中起作用。