The Upf Factor Complex Interacts with Aberrant Products Derived from mRNAs Containing a Premature Termination Codon and Facilitates Their Proteasomal Degradation

• Published in: The Journal of biological chemistry 2013-10, Vol.288 (40), p.28630-28640
• Main Authors: Kuroha, Kazushige, Ando, Koji, Nakagawa, Reiko, Inada, Toshifumi
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Codon, Nonsense - metabolism; Gene Regulation; HEK293 Cells; HSP70 Heat-Shock Proteins - metabolism; Humans; Models, Biological; mRNA Decay; Multiprotein Complexes - metabolism; Phosphoglycerate Kinase - metabolism; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Protein Folding; Protein Synthesis and Degradation; Protein Turnover; Protein Unfolding; Proteolysis; Ribosomes; RNA, Fungal - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Ubiquitination; Von Hippel-Lindau Tumor Suppressor Protein - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.460691

Up-frameshift (Upf) factors eliminate aberrant mRNAs that contain a premature termination codon (PTC). Results: The Upf complex was recruited to a PTC product and promoted the degradation of a model unfolded protein. Conclusion: Upf factors facilitate the ubiquitin-dependent degradation of products derived from mRNA containing specific PTCs. Significance: The findings reveal a mechanism of quality control that prevents the production of aberrant products derived from mRNAs containing specific PTCs. Up-frameshift (Upf) factors eliminate aberrant mRNAs containing a specific premature termination codon (PTC). Here, we show that Upf complex facilitates the ubiquitin-dependent degradation of products derived from mRNA containing specific PTCs in Saccharomyces cerevisiae. The efficiency of recruitment of the Upf complex to a PTC product was correlated with the decay of the PTC product. Upf factors promoted the degradation of the human von Hippel-Lindau (VHL) protein, which is an unfolded protein in yeast cells, in a manner that depends on the presence of a faux 3′-UTR. Mass spectrometric analysis and Western blot analysis revealed that Hsp70 was associated with the PTC product. These findings suggest that the Upf complex may be recruited to ribosomes in a faux 3′-UTR-dependent manner and then associates with aberrant products to facilitate their degradation by the proteasome.