一种慢速动态 RNA 开关调控 microRNA-21 的加工。
A Slow Dynamic RNA Switch Regulates Processing of microRNA-21.
机构信息
Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA.
Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen, Guangdong Province 518036, China.
出版信息
J Mol Biol. 2022 Aug 30;434(16):167694. doi: 10.1016/j.jmb.2022.167694. Epub 2022 Jun 23.
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) 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.
微 RNA 是非编码 RNA，可在后转录水平调节许多真核生物基因的表达，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 切割位点处发现了一种非常缓慢（0.1 s）的构象重排，该重排调节了易于和低效加工 RNA 结构状态的相对浓度。我们表明，这种动态开关受单核苷酸突变的影响，并且可以被小分子和肽配体偏向，这些配体可以指导 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。
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