TY - JOUR
T1 - Crucial role of leaky initiation of uORF3 in the downregulation of HNT1 by ER stress
AU - Matsuki, Yasuko
AU - Saito, Taishi
AU - Nakano, Yu
AU - Hashimoto, Satoshi
AU - Matsuo, Yoshitaka
AU - Inada, Toshifumi
N1 - Funding Information:
We thank the members of our 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 number JP18H03977 ).
Publisher Copyright:
© 2020 The Authors
PY - 2020/7/12
Y1 - 2020/7/12
N2 - eIF2α phosphorylation-mediated translational regulation is crucial for global repression of translation by various stresses, including the unfolded protein response (UPR) in eukaryotes. Although translational control during UPR has not been extensively investigated in S. cerevisiae, Hac1-mediated production of long transcripts containing uORFs was shown to repress the translation of histidine triad nucleotide-binding 1 (HNT1) mRNA. The present study showed that uORF3 is required for HNT1 expression, as well as down-regulating HNT1 translation. Translation initiation by uORF3 is inefficient, with uORF3 having a strong Kozak sequence efficiently repressing the translation of HNT1. We propose that leaky scanning of uORF3 is responsible for the downregulation of HNT1 during UPR.
AB - eIF2α phosphorylation-mediated translational regulation is crucial for global repression of translation by various stresses, including the unfolded protein response (UPR) in eukaryotes. Although translational control during UPR has not been extensively investigated in S. cerevisiae, Hac1-mediated production of long transcripts containing uORFs was shown to repress the translation of histidine triad nucleotide-binding 1 (HNT1) mRNA. The present study showed that uORF3 is required for HNT1 expression, as well as down-regulating HNT1 translation. Translation initiation by uORF3 is inefficient, with uORF3 having a strong Kozak sequence efficiently repressing the translation of HNT1. We propose that leaky scanning of uORF3 is responsible for the downregulation of HNT1 during UPR.
KW - Leaky initiation
KW - Translational control
KW - Unfolded protein response (UPR)
KW - uORF
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U2 - 10.1016/j.bbrc.2020.04.104
DO - 10.1016/j.bbrc.2020.04.104
M3 - Article
C2 - 32475637
AN - SCOPUS:85085315311
SN - 0006-291X
VL - 528
SP - 186
EP - 192
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -