RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site.
RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site.
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DOI：
10.1016/j.celrep.2021.109934
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发表时间：
2021-11-02
期刊：
影响因子：
8.8
通讯作者：
Chaluvally-Raghavan P
中科院分区：
文献类型：
--
作者：
George J;Li Y;Kadamberi IP;Parashar D;Tsaih SW;Gupta P;Geethadevi A;Chen C;Ghosh C;Sun Y;Mittal S;Ramchandran R;Rui H;Lopez-Berestein G;Rodriguez-Aguayo C;Leone G;Rader JS;Sood AK;Dey M;Pradeep S;Chaluvally-Raghavan P
脆性X相关蛋白-1（FXR 1）基因在卵巢癌患者中高度扩增，这种扩增与FXR 1 mRNA和蛋白表达的增加有关。FXR 1的表达与癌细胞的存活和增殖直接相关。翻译表面传感（SUnSET）测定表明，FXR 1增强癌细胞中的整体翻译。反相蛋白阵列（RPPA）显示cMYC是FXR 1的关键靶点。从机制上讲，FXR 1与cMYC的3′非翻译区（3′UTR）内存在的富含AU的元件（ARE）结合，并稳定其表达。此外，FXR 1中的RGG结构域与eIF 4A 1和eIF 4 E蛋白相互作用。FXR 1的这两种相互作用导致cMYC mRNA的环化，并促进真核生物翻译起始因子向翻译起始位点的募集。简而言之，我们发现了FXR 1促进癌细胞中cMYC水平的机制。乔治等人证明，FXR 1与MYC mRNA的3′UTR内的战神结合并提高其稳定性。作者还表明，FXR 1的RGG结构域与eIF 4A 1和eIF 4 E相互作用，并促进eIF 4F复合物募集到cMYC翻译的翻译起始位点。
Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3′ untranslated region (3′UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover a mechanism by which FXR1 promotes cMYC levels in cancer cells. George et al. demonstrate that FXR1 binds to the AREs within the 3′UTR of MYC mRNA and improves its stability. The authors also show that the RGG domain of FXR1 interacts with eIF4A1 and eIF4E and facilitates recruitment of the eIF4F complex to translation initiation sites for cMYC translation.
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脆性 X 相关蛋白 1 (FXR1) 调节母胎界面的环氧合酶 2 (COX-2) 表达
影响因子：
1.9
作者：
Li, Xiao-Cui;Song, Meng-fan;Chen, Jin-Hong
通讯作者：
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影响因子：
50.3
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通讯作者：
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影响因子：
16.6
作者：
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通讯作者：
Schneider RJ
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
8.8
作者：
Parashar, Deepak;Geethadevi, Anjali;Chaluvally-Raghavan, Pradeep
通讯作者：
Chaluvally-Raghavan, Pradeep