Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides.
Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides.
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DOI：
10.1093/nar/gkt352
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发表时间：
2013-07
影响因子：
14.9
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Zhou Y;Kierzek E;Loo ZP;Antonio M;Yau YH;Chuah YW;Geifman-Shochat S;Kierzek R;Chen G
三链是一种重要的RNA三级结构基序，在双链和第三链之间形成连续的非规范碱基对。RNA双工区也是蛋白质结合的重要功能位点。因此，三聚体形成的寡核苷酸（TFOs）可能被开发来调节涉及RNA的各种生物学功能，如病毒核糖体移框和逆转录。然而，tfo中的化学修饰如何影响RNA三联体的稳定性尚不清楚。在这里，我们将锁定的核酸、2-硫代U-和2 ' - o甲基修饰残基加入到一系列全嘧啶RNA TFOs中，并研究了它们与两种RNA发夹结构的结合。在RNA/DNA发夹的双工区和互补的RNA TFOs之间形成12碱基三主槽嘧啶-嘌呤-嘧啶三联体结构。紫外吸收检测热熔融研究表明，锁定的核酸和2-硫代U修饰在TFOs中强烈增强了与亲本RNA和DNA双工区域的三联体形成。此外，我们发现，在TFO中掺入2 ' -O甲基修饰残基，分别破坏了RNA和DNA双工区形成三联体的稳定性和稳定性。通过调节范德华接触、碱基堆叠、氢键、主链预组织、几何相容性和/或脱水能，可以促进RNA三络合物形成的（去）稳定。更好地了解RNA三联体结构稳定性的分子决定因素为设计和发现新的序列特异性双结合配体作为靶向RNA的诊断和治疗药物奠定了基础。
Triplex is emerging as an important RNA tertiary structure motif, in which consecutive non-canonical base pairs form between a duplex and a third strand. RNA duplex region is also often functionally important site for protein binding. Thus, triplex-forming oligonucleotides (TFOs) may be developed to regulate various biological functions involving RNA, such as viral ribosomal frameshifting and reverse transcription. How chemical modification in TFOs affects RNA triplex stability, however, is not well understood. Here, we incorporated locked nucleic acid, 2-thio U- and 2′-O methyl-modified residues in a series of all pyrimidine RNA TFOs, and we studied the binding to two RNA hairpin structures. The 12-base-triple major-groove pyrimidine–purine–pyrimidine triplex structures form between the duplex regions of RNA/DNA hairpins and the complementary RNA TFOs. Ultraviolet-absorbance-detected thermal melting studies reveal that the locked nucleic acid and 2-thio U modifications in TFOs strongly enhance triplex formation with both parental RNA and DNA duplex regions. In addition, we found that incorporation of 2′-O methyl-modified residues in a TFO destabilizes and stabilizes triplex formation with RNA and DNA duplex regions, respectively. The (de)stabilization of RNA triplex formation may be facilitated through modulation of van der Waals contact, base stacking, hydrogen bonding, backbone pre-organization, geometric compatibility and/or dehydration energy. Better understanding of the molecular determinants of RNA triplex structure stability lays the foundation for designing and discovering novel sequence-specific duplex-binding ligands as diagnostic and therapeutic agents targeting RNA.
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DOI：
10.1073/pnas.0905046106
发表时间：
2009-08-04
影响因子：
11.1
作者：
Chen, Gang;Chang, Kung-Yao;Tinoco, Ignacio, Jr.
通讯作者：
Tinoco, Ignacio, Jr.
影响因子：
14.9
作者：
Holland, JA;Hoffman, DW
通讯作者：
Hoffman, DW
影响因子：
3.3
作者：
Chen, Gang;Kierzek, Ryszard;Kennedy, Scott D.
通讯作者：
Kennedy, Scott D.
影响因子：
14.9
作者：
ESCUDE, C;FRANCOIS, JC;HELENE, C
通讯作者：
HELENE, C
影响因子：
3.3
作者：
Lee, Hui-Ting;Arciniegas, Santiago;Marky, Luis A.
通讯作者：
Marky, Luis A.