Interplay between PTB and miR-1285 at the p53 3'UTR modulates the levels of p53 and its isoform Δ40p53α.
Interplay between PTB and miR-1285 at the p53 3'UTR modulates the levels of p53 and its isoform Δ40p53α.
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DOI：
10.1093/nar/gkx630
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发表时间：
2017-09-29
影响因子：
14.9
通讯作者：
Das S
中科院分区：
文献类型：
--
作者：
Katoch A;George B;Iyyappan A;Khan D;Das S
p53及其翻译异构体Δ 40 p53参与细胞周期、细胞增殖、分化和代谢等重要的细胞功能。两种亚型的表达可以在不同的步骤进行调节。在本研究中，我们探讨了3′UTR在调控这两种翻译异构体表达中的作用。我们报道了反式作用因子多聚嘧啶结合蛋白（Polypyrimidine Tract Binding protein，PTB）也与p53 mRNA的3′UTR特异性相互作用，并正调控p53亚型的表达。我们的研究结果表明，在正常和应激条件下，如DNA损伤，在3′UTR的miRNA和PTB之间存在相互作用。有趣的是，PTB在p53 3 3′UTR与miR-1285的结合区域存在重叠。事实上，miR-1285的敲除以及具有突变的miR-1285结合位点的p53 3 3′UTR的表达导致PTB与3′UTR的结合增强，这提供了这种相互作用的机制见解。综上所述，这些结果为miRNAs和PTB蛋白在3′UTR的相互作用如何在微调两种p53亚型的表达中发挥关键作用提供了合理的分子基础。
p53 and its translational isoform Δ40p53 are involved in many important cellular functions like cell cycle, cell proliferation, differentiation and metabolism. Expression of both the isoforms can be regulated at different steps. In this study, we explored the role of 3′UTR in regulating the expression of these two translational isoforms. We report that the trans acting factor, Polypyrimidine Tract Binding protein (PTB), also interacts specifically with 3′UTR of p53 mRNA and positively regulates expression of p53 isoforms. Our results suggest that there is interplay between miRNAs and PTB at the 3′UTR under normal and stress conditions like DNA damage. Interestingly, PTB showed some overlapping binding regions in the p53 3′UTR with miR-1285. In fact, knockdown of miR-1285 as well as expression of p53 3′UTR with mutated miR-1285 binding sites resulted in enhanced association of PTB with the 3′UTR, which provides mechanistic insights of this interplay. Taken together, the results provide a plausible molecular basis of how the interplay between miRNAs and the PTB protein at the 3′UTR can play pivotal role in fine tuning the expression of the two p53 isoforms.
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