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Bulges control pri-miRNA processing in a position and strand-dependent manner
RNA Biology ( IF 3.6 ) Pub Date : 2020-12-31 , DOI: 10.1080/15476286.2020.1868139
Shaohua Li 1 , Thi Nhu-Y Le 1 , Trung Duc Nguyen 1 , Tam Anh Trinh 1 , Tuan Anh Nguyen 1
Affiliation  

ABSTRACT

MicroRNAs (miRNAs) play critical roles in gene expression and numerous human diseases. The success of miRNA biogenesis is largely determined by the primary miRNA (pri-miRNA) processing by the DROSHA-DGCR8 complex, called Microprocessor. Here, we analysed the high-throughput pri-miRNA processing assays and secondary structures of pri-miRNAs to investigate the roles of bulges in the pri-miRNA processing. We found that bulges in multiple places control both the cleavage efficiency and accuracy of pri-miRNA processing. These bulges were shown to act on Microprocessor via its catalytic subunit, DROSHA, and function in a position and strand-dependent manner. Interestingly, we discovered that the enriched and conserved bulges, called midB, can correct DROSHA orientation on pri-miRNAs, thereby enhancing production of miRNAs. The revealed functions of the bulges help improve our understanding of pri-miRNA processing and suggest their potential roles in miRNA biogenesis regulation.



中文翻译:

凸起以位置和链依赖性方式控制 pri-miRNA 加工

摘要

MicroRNAs (miRNAs) 在基因表达和许多人类疾病中发挥着关键作用。miRNA 生物发生的成功很大程度上取决于 DROSHA-DGCR8 复合体(称为微处理器)对初级 miRNA(pri-miRNA)的处理。在这里,我们分析了高通量 pri-miRNA 加工分析和 pri-miRNA 的二级结构,以研究凸起在 pri-miRNA 加工中的作用。我们发现多个地方的凸起控制了 pri-miRNA 加工的切割效率和准确性。这些凸起通过其催化亚基 DROSHA 作用于微处理器,并以位置和链依赖的方式发挥作用。有趣的是,我们发现被称为 midB 的富集和保守的凸起可以纠正 pri-miRNA 上的 DROSHA 方向,从而增强 miRNA 的产生。

更新日期:2020-12-31
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