In the process of the unfolded protein response (UPR), the Hac1p protein is induced through a complex regulation of the HAC1 mRNA. This includes the mRNA localization on the endoplasmic reticulum (ER) membrane and stress-triggered splicing. In yeast, a specific ribosome ubiquitination process, the monoubiquitination of eS7A by the E3 ligase Not4, facilitates the translation of HAC1ⁱ, a spliced form of the HAC1 mRNA. Upon UPR, the mono-ubiquitination of eS7A increases due to the downregulation of Ubp3, a deubiquitinating enzyme of eS7A. However, the exact mechanisms behind these regulations have remained unknown. In this study, an E3 ligase, Grr1, an F-box protein component of the SCF ubiquitin ligase complex, which is responsible for Ubp3 degradation, has been identified. Grr1-mediated Ubp3 degradation is required to maintain the level of eS7A monoubiquitination that facilitates Hac1p translation depending on the ORF of HAC1ⁱ. Grr1 also facilitates the splicing of HAC1^u mRNA independently of Ubp3 and eS7A ubiquitination. Finally, we propose distinct roles of Grr1 upon UPR, HAC1^u splicing, and HAC1ⁱ mRNA translation. Grr1-mediated Ubp3 degradation is crucial for HAC1ⁱ mRNA translation, highlighting the crucial role of ribosome ubiquitination in translational during UPR.

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Journal Article

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Sato N, Nakano Y, Matsuki Y, Tomomatsu S, Li S, Matsuo Y, Inada T

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