Bühler Marc, Wilkinson Miles F, Mühlemann Oliver
Institute of Cell Biology, University of Bern, Baltzerstrasse-4, Switzerland.
EMBO Rep. 2002 Jul;3(7):646-51. doi: 10.1093/embo-reports/kvf129.
Most vertebrate mRNAs with premature termination codons (PTCs) are specifically recognized and degraded by a process referred to as nonsense-mediated mRNA decay (NMD) while still associated with the nucleus. However, it is still a matter of debate whether PTCs can be identified by intranuclear scanning or only by ribosomes on the cytoplasmic side of the nuclear envelope. Here we show that inhibition of mRNA export by two independent approaches does not affect the downregulation of PTC-containing T-cell receptor beta transcripts in the nuclear fraction of mammalian cells, providing strong evidence for intranuclear NMD. Our results are fully consistent with recently reported evidence for nuclear translation and suggest that an important biological role for nuclear ribosomes is the early elimination of nonsense mRNA during a pioneer round of translation.
大多数带有提前终止密码子（PTC）的脊椎动物信使核糖核酸（mRNA）在仍与细胞核相关联时，会通过一种称为无义介导的mRNA降解（NMD）的过程被特异性识别并降解。然而，PTC是通过核内扫描识别，还是仅由核膜细胞质一侧的核糖体识别，仍是一个有争议的问题。在这里，我们表明，通过两种独立的方法抑制mRNA输出，并不会影响哺乳动物细胞核部分中含PTC的T细胞受体β转录本的下调，这为核内NMD提供了有力证据。我们的结果与最近报道的核翻译证据完全一致，并表明核核糖体的一个重要生物学作用是在第一轮翻译过程中早期清除无义mRNA。
