TY - JOUR
T1 - Ribosomal protein S7 ubiquitination during ER stress in yeast is associated with selective mRNA translation and stress outcome
AU - Matsuki, Yasuko
AU - Matsuo, Yoshitaka
AU - Nakano, Yu
AU - Iwasaki, Shintaro
AU - Yoko, Hideyuki
AU - Udagawa, Tsuyoshi
AU - Li, Sihan
AU - Saeki, Yasushi
AU - Yoshihisa, Tohru
AU - Tanaka, Keiji
AU - Ingolia, Nicholas T.
AU - Inada, Toshifumi
N1 - Funding Information:
The authors thank the members of their laboratories for discussions and critical comments on the manuscript. This study was supported by a Grant-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science (Grant numbers 18H03977 and 19H05281 to T.I., and 19K06481 to Y.M.), and the Uehara Memorial Foundation (to T.I.) and the Suzuken Memorial Foundation (to T.U.).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - eIF2α phosphorylation-mediated translational regulation is crucial for global translation repression by various stresses, including the unfolded protein response (UPR). However, translational control during UPR has not been demonstrated in yeast. This study investigated ribosome ubiquitination-mediated translational controls during UPR. Tunicamycin-induced ER stress enhanced the levels of ubiquitination of the ribosomal proteins uS10, uS3 and eS7. Not4-mediated monoubiquitination of eS7A was required for resistance to tunicamycin, whereas E3 ligase Hel2-mediated ubiquitination of uS10 was not. Ribosome profiling showed that the monoubiquitination of eS7A was crucial for translational regulation, including the upregulation of the spliced form of HAC1 (HAC1i) mRNA and the downregulation of Histidine triad NucleoTide-binding 1 (HNT1) mRNA. Downregulation of the deubiquitinating enzyme complex Upb3-Bre5 increased the levels of ubiquitinated eS7A during UPR in an Ire1-independent manner. These findings suggest that the monoubiquitination of ribosomal protein eS7A plays a crucial role in translational controls during the ER stress response in yeast.
AB - eIF2α phosphorylation-mediated translational regulation is crucial for global translation repression by various stresses, including the unfolded protein response (UPR). However, translational control during UPR has not been demonstrated in yeast. This study investigated ribosome ubiquitination-mediated translational controls during UPR. Tunicamycin-induced ER stress enhanced the levels of ubiquitination of the ribosomal proteins uS10, uS3 and eS7. Not4-mediated monoubiquitination of eS7A was required for resistance to tunicamycin, whereas E3 ligase Hel2-mediated ubiquitination of uS10 was not. Ribosome profiling showed that the monoubiquitination of eS7A was crucial for translational regulation, including the upregulation of the spliced form of HAC1 (HAC1i) mRNA and the downregulation of Histidine triad NucleoTide-binding 1 (HNT1) mRNA. Downregulation of the deubiquitinating enzyme complex Upb3-Bre5 increased the levels of ubiquitinated eS7A during UPR in an Ire1-independent manner. These findings suggest that the monoubiquitination of ribosomal protein eS7A plays a crucial role in translational controls during the ER stress response in yeast.
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U2 - 10.1038/s41598-020-76239-3
DO - 10.1038/s41598-020-76239-3
M3 - Article
C2 - 33184379
AN - SCOPUS:85095950081
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 19669
ER -