Translational co-regulation of a ligand and inhibitor by a conserved RNA element.
Translational co-regulation of a ligand and inhibitor by a conserved RNA element.
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DOI：
10.1093/nar/gkx938
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发表时间：
2018-01-09
影响因子：
14.9
通讯作者：
Sampath K
中科院分区：
文献类型：
--
作者：
Zaucker A;Nagorska A;Kumari P;Hecker N;Wang Y;Huang S;Cooper L;Sivashanmugam L;VijayKumar S;Brosens J;Gorodkin J;Sampath K
在许多生物体中，已经报道了对途径或过程的组成部分的转录和转录后调节。然而，到目前为止，很少有关于发育信号通路的多个组成部分的翻译共同调节的报道。在这里，我们发现了一个RNA元件，我们以前发现在斑马鱼结节相关的1/斜视(ndr1/SQT)配体mRNA的3‘UTR区中的一个背部定位元件(DLE)，被相关的配体结点相关的2/cyops(NDR2/cyc)和节点抑制因子lefty1(Lft1)和lefty2mRNAs所共享。我们在活体斑马鱼胚胎中通过功能分析研究了DLEs的活性。Lft1 DLE定位荧光标记的RNA类似于ndr1/SQT DLE。与ndr1/SQT 3‘UTR类似，lft1和lft2 3’UTRs由RNA结合蛋白(RBP)和翻译抑制因子Y盒结合蛋白1(YBX1)结合，而DLE中的缺失取消了与YBX1的结合。对斑马鱼YBX1突变体的分析表明，YBX1抑制胚胎中Lefty1的翻译。CRISPR/Cas9介导的人YBX1失活也导致人节点翻译抑制，表明DLE RNA元件/YBX1 RBP模块在调控Nodal信号方面具有更广泛的保守性。我们的发现表明，信号通路的组成部分由一个在序列和结构上保守的RNA元件和一个RBP在翻译上共同调节，揭示了一个“翻译调节子”。
In many organisms, transcriptional and post-transcriptional regulation of components of pathways or processes has been reported. However, to date, there are few reports of translational co-regulation of multiple components of a developmental signaling pathway. Here, we show that an RNA element which we previously identified as a dorsal localization element (DLE) in the 3′UTR of zebrafish nodal-related1/squint (ndr1/sqt) ligand mRNA, is shared by the related ligand nodal-related2/cyclops (ndr2/cyc) and the nodal inhibitors, lefty1 (lft1) and lefty2 mRNAs. We investigated the activity of the DLEs through functional assays in live zebrafish embryos. The lft1 DLE localizes fluorescently labeled RNA similarly to the ndr1/sqt DLE. Similar to the ndr1/sqt 3′UTR, the lft1 and lft2 3′UTRs are bound by the RNA-binding protein (RBP) and translational repressor, Y-box binding protein 1 (Ybx1), whereas deletions in the DLE abolish binding to Ybx1. Analysis of zebrafish ybx1 mutants shows that Ybx1 represses lefty1 translation in embryos. CRISPR/Cas9-mediated inactivation of human YBX1 also results in human NODAL translational de-repression, suggesting broader conservation of the DLE RNA element/Ybx1 RBP module in regulation of Nodal signaling. Our findings demonstrate translational co-regulation of components of a signaling pathway by an RNA element conserved in both sequence and structure and an RBP, revealing a ‘translational regulon’.
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影响因子：
14.9
作者：
Hecker N;Christensen-Dalsgaard M;Seemann SE;Havgaard JH;Stadler PF;Hofacker IL;Nielsen H;Gorodkin J
通讯作者：
Gorodkin J
影响因子：
11.4
作者：
Bullock, SL;Zicha, D;Ish-Horowicz, D
通讯作者：
Ish-Horowicz, D
DOI：
10.1073/pnas.1219988110
发表时间：
2013-04-02
影响因子：
11.1
作者：
Hajdin, Christine E.;Bellaousov, Stanislav;Weeks, Kevin M.
通讯作者：
Weeks, Kevin M.
影响因子：
5.8
作者：
Andronescu, Mirela;Condon, Anne;Murphy, Kevin P.
通讯作者：
Murphy, Kevin P.
影响因子：
56.9
作者：
Giraldez, AJ;Mishima, Y;Schier, AF
通讯作者：
Schier, AF