Division of Life Science, The Hong Kong University of Science & Technology, Hong Kong, China.
RNA Biol. 2021 Nov;18(11):1716-1726. doi: 10.1080/15476286.2020.1868139. Epub 2020 Dec 31.
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.
MicroRNAs (miRNAs) 在基因表达和许多人类疾病中发挥着关键作用。miRNA 的生物发生的成功在很大程度上取决于初级 miRNA (pri-miRNA) 被 DROSHA-DGCR8 复合物（称为 Microprocessor）加工。在这里，我们分析了高通量 pri-miRNA 加工测定和 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，多个位置的凸起既控制 pri-miRNA 加工的切割效率又控制切割准确性。这些凸起通过其催化亚基 DROSHA 作用于 Microprocessor，并以位置和链依赖性方式发挥作用。有趣的是，我们发现丰富且保守的凸起（称为 midB）可以校正 pri-miRNA 上 DROSHA 的取向，从而增强 miRNA 的产生。所揭示的凸起功能有助于提高我们对 pri-miRNA 加工的理解，并表明它们在 miRNA 生物发生调控中的潜在作用。
