Post-transcriptional control of executioner caspases by RNA-binding proteins.

Post-transcriptional control of executioner caspases by RNA-binding proteins.
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DOI:
10.1101/gad.285726.116
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发表时间:
2016-10-01
影响因子:
10.5
通讯作者:
Hengartner MO
Hengartner MO
中科院分区:
生物学1区
文献类型:
--
作者:
Subasic D;Stoeger T;Eisenring S;Matia-González AM;Imig J;Zheng X;Xiong L;Gisler P;Eberhard R;Holtackers R;Gerber AP;Pelkmans L;Hengartner MO

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在这项研究中,Subasic等人研究了半胱天冬酶的转录后控制。作者描述了四种保守的RNA结合蛋白(RBP),它们在C. elegans种系中,并确定了七个RBP,调节人caspase-3的表达和/或激活,这表明RBP的翻译抑制刽子手caspase可能是一个普遍的策略广泛使用的动物王国,以控制细胞凋亡。半胱天冬酶是凋亡途径的关键组分。半胱天冬酶的调节发生在几个水平,包括转录、蛋白水解加工、酶功能的抑制和蛋白质降解。相比之下,很少有人知道的caspase的转录后控制的程度。在这里,我们描述了四个保守的RNA结合蛋白(RBP)-PUF-8,MEX-3,GLD-1,CGH-1-依次抑制CED-3半胱天冬酶在不同地区的秀丽隐杆线虫种系。我们证明,GLD-1通过其3′非翻译区(UTR)的两个结合位点抑制ced-3 mRNA的翻译,从而确保在p53/CEP-1水平和执行者caspase水平双重控制不必要的细胞死亡。此外,我们鉴定了7种调节人胱天蛋白酶-3表达和/或活化的RBP,包括人PUF-8、GLD-1和CGH-1同源物RP 1、QKI和DDX 6。鉴于在许多后生动物中存在异常长的执行胱天蛋白酶3′ UTR,通过RBP对执行胱天蛋白酶的翻译控制可能是在动物界广泛使用的控制细胞凋亡的策略。
In this study, Subasic et al. investigated the post-transcriptional control of caspases. The authors describe four conserved RNA-binding proteins (RBPs) that sequentially repress the CED-3 caspase in distinct regions of the C. elegans germline and identify seven RBPs that regulate human caspase-3 expression and/or activation, suggesting that translational inhibition of executioner caspases by RBPs might be a general strategy used widely across the animal kingdom to control apoptosis. Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)—PUF-8, MEX-3, GLD-1, and CGH-1—that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3′ untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3′ UTRs in many metazoans, translational control of executioner caspases by RBPs might be a strategy used widely across the animal kingdom to control apoptosis.
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