A G-quadruplex structure within the 5'-UTR of TRF2 mRNA represses translation in human cells.
A G-quadruplex structure within the 5'-UTR of TRF2 mRNA represses translation in human cells.
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DOI：
10.1093/nar/gkq563
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发表时间：
2010-11
影响因子：
14.9
通讯作者：
Calsou P
中科院分区：
文献类型：
--
作者：
Gomez D;Guédin A;Mergny JL;Salles B;Riou JF;Teulade-Fichou MP;Calsou P
端粒保护染色体末端不被识别为双链断裂。端粒功能由shelterin复合物确保，其中TRF 2蛋白是重要的参与者。端粒DNA的富G链可以折叠成G-四链体（G4）结构。稳定G4结构的小分子，称为G4配体，已被证明可以改变人类细胞中的端粒功能。在这项研究中，我们发现，位于TRF 2 mRNA的5′-UTR区域的富含鸟嘌呤的RNA序列（以下称为91 TRF 2G）能够形成稳定的四链体，与不能折叠成G4的突变体5′-UTR相比，该四链体导致人类细胞中报告基因的翻译减少2.8倍。我们还证明了几种高选择性的G4配体，吡啶二甲酰胺衍生物360 A和双喹啉化合物Phen-DC（3）和Phen-DC（6），能够结合91 TRF 2G：RNA序列并在体外调节TRF 2蛋白翻译。由于本文使用了在几种脊椎动物直向同源物中保守的天然存在的5′-UTR TRF 2：RNA G4元件，因此本数据证实了由G4 RNA基序介导的下调TRF 2表达的潜在翻译机制。
Telomeres protect chromosome ends from being recognized as double-stranded breaks. Telomeric function is ensured by the shelterin complex in which TRF2 protein is an essential player. The G-rich strand of telomere DNA can fold into G-quadruplex (G4) structure. Small molecules stabilizing G4 structures, named G4 ligands, have been shown to alter telomeric functions in human cells. In this study, we show that a guanine-rich RNA sequence located in the 5′-UTR region of the TRF2 mRNA (hereafter 91TRF2G) is capable of forming a stable quadruplex that causes a 2.8-fold decrease in the translation of a reporter gene in human cells, as compared to a mutant 5′-UTR unable to fold into G4. We also demonstrate that several highly selective G4 ligands, the pyridine dicarboxamide derivative 360A and bisquinolinium compounds Phen-DC(3) and Phen-DC(6), are able to bind the 91TRF2G:RNA sequence and to modulate TRF2 protein translation in vitro. Since the naturally occurring 5′-UTR TRF2:RNA G4 element was used here, which is conserved in several vertebrate orthologs, the present data substantiate a potential translational mechanism mediated by a G4 RNA motif for the downregulation of TRF2 expression.
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影响因子：
14.9
作者：
Gomez, D;Lemarteleur, T;Riou, JF
通讯作者：
Riou, JF
G-四链体配体与人染色体末端的优先结合。
影响因子：
14.9
作者：
Granotier, C;Pennarun, G;Riou, L;Hoffschir, F;Gauthier, LR;De Cian, A;Gomez, D;Mandine, E;Riou, JF;Mergny, JL;Mailliet, P;Dutrillaux, B;Boussin, FD
通讯作者：
Boussin, FD
影响因子：
3.2
作者：
Bugaut A;Rodriguez R;Kumari S;Hsu ST;Balasubramanian S
通讯作者：
Balasubramanian S
影响因子：
14.9
作者：
Halder K;Wieland M;Hartig JS
通讯作者：
Hartig JS
影响因子：
8.4
作者：
Biroccio, Annamaria;Rizzo, Angela;Gilson, Eric
通讯作者：
Gilson, Eric