Decoding of OAZ1 (Ornithine decarboxylase AntiZyme 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.

中文翻译：

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核糖体相关质量控制介导 ODC 抗酶 mRNA 过早翻译终止产物 Orf1p 的降解

的解码OAZ1（ø rnithine脱羧酶甲NTI žyme 1) mRNA 包含两个开放阅读框（ORF1 和 ORF2），被自然发生的过早终止密码子 (PTC) 打断，产生一个 8 kDa 截短的多肽，称为 Orf1p，除非 PTC 被 +1 核糖体移码绕过。在这项研究中，我们将 Orf1p 鉴定为酵母和哺乳动物细胞中 26S 蛋白酶体的内源性泛素依赖性底物。令人惊讶的是，我们发现核糖体相关质量控制因子 Rqc1 和泛素连接酶 Ltn1 对 Orf1p 降解至关重要。此外，Orf1p 蛋白水解还需要细胞质蛋白质量控制伴侣系统 Hsp70/Hsp90 及其相应的辅助伴侣 Sse1、Fes1、Sti1 和 Cpr7。我们的研究发现，由于过早的翻译终止事件而自然合成的 Orf1p，