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.

eIF2α磷酸化介导的翻译调控对于各种压力（包括真核生物中未折叠的蛋白质反应（UPR））导致的整体翻译抑制至关重要。尽管尚未在啤酒酵母中广泛研究UPR期间的翻译控制，但显示Hac1介导的包含uORF的长转录产物的产生可抑制组氨酸三联体核苷酸结合1（HNT1）mRNA的翻译。本研究表明，uORF3是HNT1表达以及下调HNT1翻译所必需的。uORF3的翻译启动效率低下，uORF3具有强大的Kozak序列，可有效抑制HNT1的翻译。我们建议uORF3的泄漏扫描导致UPR期间HNT1的下调。