PDF(Sci-hub)
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起着关键作用。miRNA生物发生的成功很大程度上取决于DROSHA-DGCR8复合物的初级miRNA（pri-miRNA）加工，叫做微处理器。这里,我们分析了高通量pri-miRNA加工试验和pri-miRNA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控制pri-miRNA处理的切割效率和准确性。这些凸起被证明通过其催化亚基作用于微处理器，Drosha,并以位置和链依赖的方式发挥作用。有趣的是,我们发现丰富和保守的凸起，叫做midB，可以纠正pri-miRNAs上的DROSHA方向，从而增强miRNA的产生。凸起的显示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。
