Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14 Str, 61-704, Poznan, Poland.
Cell Mol Life Sci. 2011 Sep;68(17):2859-71. doi: 10.1007/s00018-011-0726-2. Epub 2011 May 24.
The human genome contains more than 1,000 microRNA (miRNA) genes, which are transcribed mainly by RNA polymerase II. The canonical pathway of miRNA biogenesis includes the nuclear processing of primary transcripts (pri-miRNAs) by the ribonuclease Drosha and further cytoplasmic processing of pre-miRNAs by the ribonuclease Dicer. This review discusses the issue of miRNA end heterogeneity generated primarily by Drosha and Dicer cleavage and focuses on the structural aspects of the Dicer step of miRNA biogenesis. We examine the structures of miRNA precursors, both predicted and experimentally determined, as well as the influence of various motifs that disturb the regularity of pre-miRNA structure on Dicer cleavage specificity. We evaluate the structural determinants of the length diversity of miRNA generated by Dicer from different precursors and highlight the importance of asymmetrical motifs. Finally, we discuss the impact of Dicer protein partners on cleavage efficiency and specificity and propose the contribution of pre-miRNA structural plasticity to the dynamics of the dicing complex.
人类基因组包含超过 1000 个 microRNA（miRNA）基因，这些基因主要由 RNA 聚合酶 II 转录。miRNA 生物发生的典型途径包括核内核糖核酸酶 Drosha 对初级转录物（pri-miRNAs）的加工，以及细胞质内核糖核酸酶 Dicer 对 pre-miRNAs 的进一步加工。本文讨论了主要由 Drosha 和 Dicer 切割产生的 miRNA 末端异质性问题，并重点关注 miRNA 生物发生中 Dicer 步骤的结构方面。我们检查了 miRNA 前体的结构，包括预测的和实验确定的，以及各种破坏 pre-miRNA 结构规律性的模体对 Dicer 切割特异性的影响。我们评估了由不同前体的 Dicer 产生的 miRNA 长度多样性的结构决定因素，并强调了不对称模体的重要性。最后，我们讨论了 Dicer 蛋白伴侣对切割效率和特异性的影响，并提出了 pre-miRNA 结构可塑性对切割复合物动力学的贡献。
