Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
Genes Dev. 2023 Jun 1;37(11-12):474-489. doi: 10.1101/gad.350752.123. Epub 2023 Jul 11.
In addition to the main, protein-coding, open reading frame (mORF), many eukaryotic mRNAs contain upstream ORFs (uORFs) initiated at AUG or near-cognate codons residing 5' of the mORF start site. Whereas translation of uORFs generally represses translation of the mORFs, a subset of uORFs serves as a nexus for regulating translation of the mORF. In this review, we summarize the mechanisms by which uORFs can repress or stimulate mRNA translation, highlight uORF-mediated translational repression involving ribosome queuing, and critically evaluate recently described alternatives to the delayed reinitiation model for uORF-mediated regulation of the / mRNAs.
除了主要的、蛋白质编码的开放阅读框 (mORF) 外,许多真核 mRNA 还包含起始于 AUG 或 mORF 起始位点 5' 处附近的同义密码子的上游开放阅读框 (uORF)。虽然 uORF 的翻译通常会抑制 mORF 的翻译,但一部分 uORF 作为调节 mORF 翻译的枢纽。在这篇综述中,我们总结了 uORF 抑制或刺激 mRNA 翻译的机制,重点介绍了涉及核糖体排队的 uORF 介导的翻译抑制,并批判性地评价了最近描述的替代延迟重新起始模型来解释 uORF 对 / mRNAs 的调节作用。