小分子核糖核酸（miRNA）属于一类存在于几乎所有植物和动物中的长度约为22个核苷酸的小非编码核糖核酸。miRNA的准确表达和序列保真是由miRNA生物合成过程决定的，在基因表达调控中发挥关键作用。在人体中，Microprocessor蛋白复合物通过切割miRNA前体或pri-miRNA产生pre-miRNA，然后Exportin-5接过pre-miRNA并转运到细胞质中进一步剪切加工。 我们最近的工作已经解决了Microprocessor分子机制在过去十年的争议，并建立了Microprocessor作用机制的综合模型。 然而，目前还是不清楚Microprocessor如何释放剪切产物，以及剪切产物如何被Exportin-5拾起。 本课题旨在揭示Microprocessor的剪切产物释放机制和Exportin-5在该过程中的作用，从而揭示miRNA新的一层表达调控机制。

MicroRNAs (miRNAs) small non-coding RNAs (~22 nucleotides) that are present in virtually all plants and animals and play critical roles in gene expression regulation. The proper expression and sequence fidelity of miRNAs, which are largely governed by miRNA biogenesis, must be achieved for their normal functions in cells. In human, Microprocessor initiates miRNA biogenesis by cleaving miRNA precursors or pri-miRNAs to generate pre-miRNAs which are picked up by Exportin-5. Our latest work has solved the controversy of Microprocessor molecular mechanism for last decade and revealed the comprehensive model of Microprocessor mechanism. However, it has not been known how Microprocessor release the products and how the products are picked up by Exportin-5. This proposal aims to unveil the product release mechanism of Microprocessor and the roles of Exportin-5 in this process, thereby adding one more layer of regulation on miRNA expression.