A 69 nt segment in the 5'UTR regulates translation of FOXO3a under stress conditions
首发时间:2020-04-08
Abstract:Fork head box O3 (FOXO3a) is a transcription factor that mediates various fundamental cellular processes, including cell cycle progression, proliferation, DNA damage and apoptosis. This study showed that the 5\' untranslated region (5\'UTR) of FOXO3a mRNA contains an internal ribosome entry site (IRES). After mapping the 5\'UTR of FOXO3a mRNA, we found that a 69 nt sequence located between 175-243 was the key segment for the overall IRES activity. Further, we generated a knockout cell line of this 69 nt segment using CRISPR technology. During serum-starvation and ADM drug stress, the deletion of this 69 nt segment could inhibit the expression of FOXO3a to some extent in the knockout cells. These results strongly suggested that the 69 nt segment is essential for self-regulation of FOXO3a under stress conditions, and could be a potential target for the regulation of FOXO3a.
keywords: Biochemistry and Molecular Biology 5\'UTR FOXO3a IRES
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5'非翻译区中的69bp片段在应激条件下调节FOXO3a的表达翻译
摘要:叉头盒O3(FOXO3a)是一种转录因子,可介导各种基本细胞进程,包括细胞周期进程,增殖,DNA损伤和凋亡。本研究证明FOXO3a mRNA的5\'非翻译区(5\'UTR)包含内部核糖体进入位点(IRES),并且找出位于nt175-243之间的69 nt序列是IRES活性中心域。此外,我们使用CRISPR技术构建了69 nt片段的IRES活性中心敲除细胞株。在血清饥饿和ADM药物应激期间,该69 nt片段的缺失可以在一定程度上抑制敲除细胞中FOXO3a mRNA的表达翻译。这些结果证明69 nt片段对于应激条件下FOXO3a mRNA的自我调节至关重要,并且可能是调节FOXO3a mRNA表达翻译的潜在靶标。
关键词: 生物化学与分子生物学 5\'UTR FOXO3a IRES
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5'非翻译区中的69bp片段在应激条件下调节FOXO3a的表达翻译
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