Ribosome-associated quality control mediates degradation of the premature translation termination product Orf1p of ODC antizyme mRNA

FEBS Letters

article

Ashis Kumar Pradhan¹  Ganapathi Kandasamy¹  Upasana Chatterjee¹  Anushree Bharadwaj²  Sam J. Mathew²  R. Jürgen Dohmen³  R. Palanimurugan¹ 

[1] CSIR-Centre for Cellular and Molecular Biology;Regional Centre for Biotechnology, NCR Biotech Science Cluster;Institute for Genetics, Faculty of Mathematics and Natural Sciences, Center of Molecular Biosciences, University of Cologne;Deceased

关键词: antizyme;    protein degradation;    ribosomal frameshifting;    ribosome-associated protein quality control;    Ubiquitin/Proteasome System;   

DOI  :  10.1002/1873-3468.14147

来源: John Wiley & Sons Ltd.

【 摘 要 】

Decoding of OAZ1 ( O rnithine decarboxylase A nti Z yme 1) mRNA, which harbours two open reading frames (ORF1 and ORF2) interrupted by a naturally occurring Premature Termination Codon (PTC), produces an 8 kDa truncated polypeptide termed Orf1p, unless the PTC is bypassed by +1 ribosomal frameshifting. In this study, we identified Orf1p as an endogenous ubiquitin-dependent substrate of the 26S proteasome both in yeast and mammalian cells. Surprisingly, we found that the ribosome-associated quality control factor Rqc1 and the ubiquitin ligase Ltn1 are critical for Orf1p degradation. In addition, the cytosolic protein quality control chaperone system Hsp70/Hsp90 and their corresponding co-chaperones Sse1, Fes1, Sti1 and Cpr7 are also required for Orf1p proteolysis. Our study finds that Orf1p, which is naturally synthesized as a result of a premature translation termination event, requires the coordinated role of both ribosome-associated and cytosolic protein quality control factors for its degradation.

【 授权许可】

Unknown