Upf1 stimulates degradation of the product derived from aberrant messenger RNA containing a specific nonsense mutation by the proteasome.
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.
Department of Molecular Biology, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
Kazushige
K
Kuroha
Tsuyako
T
Tatematsu
Toshifumi
T
Inada
D020413:3' Untranslated Regions; D015153:Blotting, Western; D018389:Codon, Nonsense; D018388:Codon, Terminator; D015966:Gene Expression Regulation, Fungal; D008957:Models, Genetic; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D020365:RNA Helicases / Q000502:physiology*; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*
D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D018388:Codon, Terminator; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases