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Ribosome‐associated quality control mediates degradation of the premature translation termination product Orf1p of ODC antizyme mRNA
Author(s) -
Pradhan Ashis Kumar,
Kandasamy Ganapathi,
Chatterjee Upasana,
Bharadwaj Anushree,
Mathew Sam J.,
Dohmen R. Jürgen,
Palanimurugan R.
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14147
Subject(s) - ribosome , chaperone (clinical) , ornithine decarboxylase antizyme , ubiquitin ligase , biology , translational frameshift , internal ribosome entry site , messenger rna , microbiology and biotechnology , ubiquitin , biochemistry , genetics , chemistry , rna , ornithine decarboxylase , enzyme , medicine , gene , pathology
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.