B-CePs as cross-linking probes for the investigation of RNA higher-order structure.
B-CePs as cross-linking probes for the investigation of RNA higher-order structure.
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DOI：
10.1093/nar/gkab468
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发表时间：
2021-07-09
影响因子：
14.9
通讯作者：
Gatto B
中科院分区：
文献类型：
--
作者：
Sosic A;Göttlich R;Fabris D;Gatto B
阐明RNA和RNA系综的结构对于理解生物功能是必不可少的。在这项工作中，我们探索了双氯哌啶(B-CEP)对RNA的反应活性。我们在分子水平上表征了快速反应化合物B-CEP 1与RNA诱导的不同加合物。采用溶液热熔联用电喷雾质谱(STHEM-ESI)的方法，我们证明了B-CEPS能够诱导双链RNA中鸟嘌呤类物质之间的分子间交联。这些结果为利用B-CEPs作为结构探针研究高阶结构提供了可能性，例如由HIV-1基因组的二聚化起始点(DIS)建立的亲吻环复合体。我们证实了B-CEPS在揭示远程相互作用中所涉及的RNA结构的同一性方面的潜力，期望有助于对不容易服从传统高分辨率技术的样本的表征，从而促进与新旧疾病相关的RNA系统的阐明。B-CEP不怕高温！B-CEPs能够在放置在相对RNA链中的鸟嘌呤之间产生稳定的交联物，这种交联物在高温下不受影响，这为将其开发为生物相关RNA系的结构研究的特定化学探针提供了机会。
Elucidating the structure of RNA and RNA ensembles is essential to understand biological functions. In this work, we explored the previously uncharted reactivity of bis-chloropiperidines (B-CePs) towards RNA. We characterized at the molecular level the different adducts induced by the fast reacting compound B-CeP 1 with RNA. Following an approach based on solution thermal melting coupled with ESI mass spectrometry (STHEM-ESI), we proved the ability of B-CePs to induce inter-molecular cross-links between guanines in double stranded RNA. These results open the possibility of using B-CePs as structural probes for investigating higher-order structures, such as the kissing loop complex established by the dimerization initiation site (DIS) of the HIV-1 genome. We confirmed the potential of B-CePs to reveal the identity of RNA structures involved in long-range interactions, expecting to benefit the characterization of samples that are not readily amenable to traditional high-resolution techniques, and thus promoting the elucidation of pertinent RNA systems associated with old and new diseases. B-CePs do not fear high temperatures! B-CePs ability to produce stable cross-links, which remain unaffected at high temperatures, between guanines placed in opposing RNA strands opens the opportunity to develop them as specific chemical probes for structural studies of biological relevant RNA ensembles.
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影响因子：
14.9
作者：
GARRETTWHEELER, E;LOCKARD, RE;KUMAR, A
通讯作者：
KUMAR, A
影响因子：
5.4
作者：
Shen, N;Jetté, L;Laughrea, M
通讯作者：
Laughrea, M
影响因子：
3.4
作者：
Helbing T;Carraro C;Francke A;Sosic A;De Franco M;Gandin V;Göttlich R;Gatto B
通讯作者：
Gatto B
影响因子：
14.8
作者：
Kubota, Miles;Tran, Catherine;Spitale, Robert C.
通讯作者：
Spitale, Robert C.
影响因子：
5.4
作者：
Clever, JL;Parslow, TG
通讯作者：
Parslow, TG