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Visualizing a protonated RNA state that modulates microRNA-21 maturation.

可视化调节microRNA-21成熟的质子化RNA状态。

  • 影响因子:9.33
  • DOI:10.1038/s41589-020-00667-5
  • 作者列表:"Baisden JT","Boyer JA","Zhao B","Hammond SM","Zhang Q
  • 发表时间:2021-01-01
Abstract

:MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR relaxation dispersion spectroscopy and mutagenesis, we reveal that the precursor of oncogenic microRNA-21 exists as a pH-dependent ensemble that spontaneously reshuffles the secondary structure of the entire apical stem-loop region, including the Dicer cleavage site. We show that the alternative excited conformation transiently sequesters the bulged adenine into a noncanonical protonated A+-G mismatch, conferring a substantial enhancement in Dicer processing over its ground conformational state. These results indicate that microRNA maturation efficiency may be encoded in the intrinsic dynamic ensemble of primary and precursor microRNAs, providing a potential means of regulating microRNA biogenesis in response to environmental and cellular stimuli.

摘要

: MicroRNAs是进化上保守的小型非编码rna,其调节多种生物过程。由于它们的基本调节作用,microRNA生物发生受到严格调节,其中经常发现蛋白质因子与特定的初级和前体microRNA相互作用以进行调节。在这里,使用NMR弛豫色散谱和诱变,我们揭示了致癌microRNA-21的前体以pH依赖性系综的形式存在,其自发地使整个顶端茎-环区域的二级结构 (包括Dicer切割位点) 重组。我们表明,替代激发构象瞬时螯合凸起的腺嘌呤为非规范质子化的a +-G错配,赋予Dicer加工对其地面构象状态的实质性增强。这些结果表明,microRNA成熟效率可能在初级和前体microRNA的内在动态集合中编码,提供了响应环境和细胞刺激调节microRNA生物发生的潜在手段。

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DOI:10.1080/14656566.2020.1814255
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DOI:10.1007/s11033-021-06299-9
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