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.

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。