Novel RNA base pair with higher specificity using single selenium atom.

Novel RNA base pair with higher specificity using single selenium atom.
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DOI:
10.1093/nar/gks010
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发表时间:
2012-06
影响因子:
14.9
通讯作者:
Huang Z
Huang Z
中科院分区:
生物学2区
文献类型:
--
作者:
Sun H;Sheng J;Hassan AE;Jiang S;Gan J;Huang Z

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核碱基配对的特异性为生物体的遗传信息储存、复制、转录和翻译提供了重要的基础。然而,摆动碱基对,其中RNA中的U(或DNA中的T)与G而不是A配对,可能会损害碱基配对的高特异性。U/G摆动配对在RNA中普遍存在,特别是在非编码RNA中。为了增加U/A配对特异性,我们假设通过调整尿苷2-exo位置的空间和电子效应并用硒原子取代2-exo氧原子来区分U/G摆动对。本文报道了2-Se-U-RNA和2-Se-Uridine(SeU)亚磷酰胺的首次合成。我们对SeU-RNA的生物物理和结构研究表明,这种单原子取代确实可以产生一种新的U/A碱基对,其特异性高于天然碱基对。我们发现,SeU/A对保持一个结构几乎相同的天然U/A碱基对,而歧视U/G摆动对。这种用硒进行的氧置换提供了一种独特的化学策略,以增强原子水平上的碱基配对特异性。
Specificity of nucleobase pairing provides essential foundation for genetic information storage, replication, transcription and translation in all living organisms. However, the wobble base pairs, where U in RNA (or T in DNA) pairs with G instead of A, might compromise the high specificity of the base pairing. The U/G wobble pairing is ubiquitous in RNA, especially in non-coding RNA. In order to increase U/A pairing specificity, we have hypothesized to discriminate against U/G wobble pair by tailoring the steric and electronic effects at the 2-exo position of uridine and replacing the 2-exo oxygen with a selenium atom. We report here the first synthesis of the 2-Se-U-RNAs as well as the 2-Se-uridine (SeU) phosphoramidite. Our biophysical and structural studies of the SeU-RNAs indicate that this single atom replacement can indeed create a novel U/A base pair with higher specificity than the natural one. We reveal that the SeU/A pair maintains a structure virtually identical to the native U/A base pair, while discriminating against U/G wobble pair. This oxygen replacement with selenium offers a unique chemical strategy to enhance the base pairing specificity at the atomic level.
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