A dimeric RNA quadruplex architecture comprised of two G:G(:A):G:G(:A) hexads, G:G:G:G tetrads and UUUU loops
A dimeric RNA quadruplex architecture comprised of two G:G(:A):G:G(:A) hexads, G:G:G:G tetrads and UUUU loops
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DOI：
10.1016/s0022-2836(02)00876-8
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发表时间：
2002-10-04
影响因子：
5.6
通讯作者：
Uesugi, S
中科院分区：
文献类型：
--
作者：
Liu, H;Matsugami, A;Uesugi, S
使用CD和NMR，我们确定了RNA寡聚体r（GGAGGUUUGGAGG）（R14）的结构，其包含由UUUU片段连接的两个GGAGG片段。即使在K+不存在的情况下，也观察到r（GGAGGUUUGGAGG）在溶液中的改良四链体结构。本文报道了在低K+浓度下由r（GGAGGUUUGGAGG）的两条链形成的异常稳定的二聚RNA四链体结构。在r（GGAGGUUUUGGAGG）的每条链中，GGAGG片段中的两组连续的转角和UUUU环两端的转角驱动四个G-G步骤以平行方式对齐，形成具有两个堆叠的G-四联体的核心。两个腺嘌呤碱基通过剪切的G：A错配与一个G：G：G：G四分体的两个边缘结合，将四分体增强为G：G（：A）：G：G（：A）六联体。因此，r（GGAGGUUUUGGAGG）的一个分子折叠成修饰的四链体，其包含G：G：G：G四联体、UUUU双链反向环和G：G（：A）：G：G（：A）六联体。两个这样的分子通过具有旋转对称性的二聚六-六界面堆叠而进一步缔合。大多数核苷酸的核糖环带有S（靠近C2 '-endo）褶皱，这对于RNA来说是不寻常的。K+可以增加这种四链体结构的稳定性，结合的K+的数量从滴定实验的结果估计。除G：G和G：A错配外，还存在O_4 ′-NH_2和C-H等氢键网络。O氢键和广泛的碱基堆积有助于R14的高热力学稳定性。本研究结果为阐明广泛存在于各种RNA中的含GGAGG的RNA片段的生物学作用提供了立体化学和热力学基础。四链体介导的mRNA-FMRP结合和HIV-1基因组RNA二聚化的相关性进行了讨论。(C)2002爱思唯尔科技有限公司版权所有。
Using CD and NMR, we determined the structure of an RNA oligomer, r(GGAGGUUUUGGAGG) (R14), comprising two GGAGG segments joined by a UUUU segment. A modified quadruplex structure was observed for r(GGAGGUUUUGGAGG) in solution even in the absence of K+. An unusually stable dimeric RNA quadruplex architecture formed from two strands of r(GGAGGUUUUGGAGG) at low K+ concentration is reported here. In each strand of r(GGAGGUUUUGGAGG), two sets of successive turns in the GGAGG segments and turns at both ends of the UUUU loops drive four G-G steps to align in a parallel manner, a core with two stacked G-tetrads being formed. Two adenine bases bind to two edges of one G:G:G:G tetrad through the sheared G:A mismatch augmenting the tetrad into a G:G(:A):G:G(:A) hexad. Thus, one molecule of r(GGAGGUUUUGGAGG) folds into a modified quadruplex comprising a G:G:G:G tetrad, a UUUU double-chain reversal loop and a G:G(:A):G:G(:A) hexad. Two such molecules further associate by stacking through the dimeric hexad-hexad interface with a rotational symmetry. The ribose rings of most nucleotides take S (close to C2'-endo) puckering, which is unusual for an RNA. K+ can increase the stability of this quadruplex structure; the number of bound K+ was estimated from the results of the titration experiment. Besides G:G and G:A mismatches, a network of hydrogen bonds including O4'-NH2 and C-H...O hydrogen bonds, and the extensive base stacking contribute to the high thermodynamic stability of R14. Our results could provide the stereochemical and thermodynamic basis for elucidating the biological role of the GGAGG-containing RNA segments abundantly existing in various RNAs. Relevance to quadruplex-mediated mRNA-FMRP binding and HIV-1 genome RNA dimerization is discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.