Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
J Biochem. 2011 Jan;149(1):15-25. doi: 10.1093/jb/mvq113. Epub 2010 Sep 27.
MicroRNA (miRNA) modules are built in genetic networks as a complex regulatory layer directing post-transcriptional gene regulation. miRNAs coordinate a broad spectra of gene expression programs mainly through modulation of mRNA metabolism. Perturbations of miRNA networks are linked to a wide variety of pathological processes, including cardiovascular diseases and cancer. While the mechanisms regulating miRNA biogenesis were previously poorly understood, recent findings have shed light on the regulatory mechanisms of miRNAs themselves, especially their biogenesis. Multiple steps of miRNA maturation could potentially provide a variety of regulatory options to generate mature miRNAs differentially and produce gradation in miRNA processing efficiency. Several studies have demonstrated that miRNA maturation pathways crosstalk with intracellular signalling molecules, including p53, Smad proteins and estrogen receptor. Other lines of evidence have demonstrated the involvement of multiple RNA binding proteins in biased processing of different miRNA species. This review summarizes accumulating evidence for the emerging complexity and dynamics of regulated miRNA processing. These findings will lead to better understanding of miRNA dynamics in various pathogenetic pathways and provide the molecular basis for diagnostic and therapeutic strategies based on small RNA biology.
miRNA（microRNA）模块作为一个复杂的调控层，在遗传网络中构建，指导转录后基因调控。miRNAs 通过调节 mRNA 代谢，协调广泛的基因表达程序。miRNA 网络的失调与多种病理过程有关，包括心血管疾病和癌症。虽然 miRNA 生物发生的调节机制以前知之甚少，但最近的发现揭示了 miRNA 本身的调节机制，特别是它们的生物发生。miRNA 成熟的多个步骤可能为产生成熟 miRNA 的差异提供多种调控选择，并产生 miRNA 加工效率的梯度。几项研究表明，miRNA 成熟途径与包括 p53、Smad 蛋白和雌激素受体在内的细胞内信号分子相互作用。其他证据表明，多种 RNA 结合蛋白参与不同 miRNA 物种的偏向加工。本综述总结了 miRNA 加工调控不断增加的复杂性和动态的累积证据。这些发现将有助于更好地理解各种致病途径中的 miRNA 动态，并为基于小 RNA 生物学的诊断和治疗策略提供分子基础。
