A Slow Dynamic RNA Switch Regulates Processing of microRNA-21.
A Slow Dynamic RNA Switch Regulates Processing of microRNA-21.
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DOI：
10.1016/j.jmb.2022.167694
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发表时间：
2022-08-30
影响因子：
5.6
通讯作者：
Varani, Gabriele
中科院分区：
文献类型：
--
作者：
Shortridge, Matthew D.;Olsen, Greg L.;Yang, Wen;Walker, Matthew J.;Varani, Gabriele
microRNA是转录后调节许多真核基因表达的非编码RNA，其失调是人类疾病的驱动因素。在这里，我们报告了在pre-miR-21的Dicer切割位点发现的非常缓慢（0.1 s−1）的构象重排，它调节了容易加工和低效加工的RNA结构状态的相对浓度。我们发现，这种动态开关受到单核苷酸突变的影响，并且可以受到小分子和肽配体的偏置，这可以指导microRNA占据低效加工状态并降低加工效率。这一结果揭示了一种新的RNA调控机制，并提出了一种通过选择性稳定其未加工或加工状态来抑制或激活致病性microRNA的化学方法。
The microRNAs are non-coding RNAs which post-transcriptionally regulate the expression of many eukaryotic genes, and whose dysregulation is a driver of human disease. Here we report the discovery of a very slow (0.1 s−1) conformational rearrangement at the Dicer cleavage site of pre-miR-21, which regulates the relative concentration of readily- and inefficiently-processed RNA structural states. We show that this dynamic switch is affected by single nucleotide mutations and can be biased by small molecule and peptide ligands, which can direct the microRNA to occupy the inefficiently processed state and reduce processing efficiency. This result reveals a new mechanism of RNA regulation and suggests a chemical approach to suppressing or activating pathogenic microRNAs by selective stabilization of their unprocessed or processed states.
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DOI：
10.4049/jimmunol.1101235
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Hartner J;Lim EJ;Fabry V;Mingler MK;Cole ET;Orkin SH;Aronow BJ;Rothenberg ME
通讯作者：
Rothenberg ME
影响因子：
14.8
作者：
Baisden, Jared T.;Boyer, Joshua A.;Zhang, Qi
通讯作者：
Zhang, Qi
影响因子：
64.5
作者：
Han, Jinju;Lee, Yoontae;Kim, V. Narry
通讯作者：
Kim, V. Narry
影响因子：
64.8
作者：
Davis, Brandi N.;Hilyard, Aaron C.;Hata, Akiko
通讯作者：
Hata, Akiko
影响因子：
14.8
作者：
Chen Y;Yang F;Zubovic L;Pavelitz T;Yang W;Godin K;Walker M;Zheng S;Macchi P;Varani G
通讯作者：
Varani G