提前终止密码子在细胞核中以阅读框依赖的方式被识别。
Premature Termination Codons Are Recognized in the Nucleus in A Reading-Frame Dependent Manner.
作者信息
Shi Min, Zhang Heng, Wang Lantian, Zhu Changlan, Sheng Ke, Du Yanhua, Wang Ke, Dias Anusha, Chen She, Whitman Malcolm, Wang Enduo, Reed Robin, Cheng Hong
机构信息
State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Cell Discov. 2015;1:15001-. doi: 10.1038/celldisc.2015.1. Epub 2015 May 5.
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.
含有提前终止密码子（PTC）的mRNA已知会通过无义介导的mRNA降解（NMD）途径被降解。出乎意料的是，我们发现含有任何类型PTC（UAA、UAG、UGA）的mRNA会滞留在细胞核中，而它们的野生型对应物则会迅速输出。这种滞留严格依赖于阅读框。引人注目的是，我们的数据表明，在细胞核中进行翻译的核糖体能够校对阅读框并检测细胞核中的PTC。此外，穿梭NMD蛋白Upf1在细胞核中特异性地与含PTC的mRNA结合，并且是含PTC的mRNA在细胞核中滞留所必需的。总之，我们的数据得出了一个工作模型，即PTC在细胞核中被进行翻译的核糖体识别，导致Upf1的募集，进而在含PTC的mRNA的细胞核滞留中发挥作用。细胞核中对PTC的识别为mRNA增添了一层新的校对机制，对于确保蛋白质生产所需的极高保真度可能至关重要。
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