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EMBO Rep. 2009 Nov;10(11):1265-71. doi: 10.1038/embor.2009.200. Epub 2009 Oct 2.

Upf1 stimulates degradation of the product derived from aberrant messenger RNA containing a specific nonsense mutation by the proteasome.

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  • 1Department of Molecular Biology, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.


Aberrant messenger RNAs containing a premature termination codon (PTC) are eliminated by the nonsense-mediated mRNA decay (NMD) pathway. Here, we show that a crucial NMD factor, up frameshift 1 protein (Upf1), is required for rapid proteasome-mediated degradation of an aberrant protein (PTC product) derived from a PTC-containing mRNA. Western blot and pulse-chase analyses revealed that Upf1 stimulates the degradation of specific PTC products by the proteasome. Moreover, the Upf1-dependent, proteasome-mediated degradation of the PTC product was also stimulated by mRNAs harbouring a faux 3' untranslated region (3'-UTR). These results indicate that protein stability might be regulated by an aberrant mRNA 3'-UTR.

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