Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany.
Nat Rev Mol Cell Biol. 2019 Jan;20(1):5-20. doi: 10.1038/s41580-018-0059-1.
MicroRNAs (miRNAs) are short non-coding RNAs that inhibit the expression of target genes by directly binding to their mRNAs. miRNAs are transcribed as precursor molecules, which are subsequently cleaved by the endoribonucleases Drosha and Dicer. Mature miRNAs are bound by a member of the Argonaute (AGO) protein family to form the RNA-induced silencing complex (RISC) in a process termed RISC loading. Advances in structural analyses of Drosha and Dicer complexes enabled elucidation of the mechanisms that drive these molecular machines. Transcription of miRNAs, their processing by Drosha and Dicer and RISC loading are key steps in miRNA biogenesis, and various additional factors facilitate, support or inhibit these processes. Recent work has revealed that regulatory factors not only coordinate individual miRNA processing steps but also connect miRNA biogenesis with other cellular processes. Protein phosphorylation, for example, links miRNA biogenesis to various signalling pathways, and such modifications are often associated with disease. Furthermore, not all miRNAs follow canonical processing routes, and many non-canonical miRNA biogenesis pathways have recently been characterized.
微小 RNA（miRNA）是短的非编码 RNA，通过直接与靶基因的 mRNAs 结合来抑制靶基因的表达。miRNA 作为前体分子被转录，随后被内切核酸酶 Drosha 和 Dicer 切割。成熟的 miRNA 与 Argonaute（AGO）蛋白家族的成员结合，在称为 RISC 加载的过程中形成 RNA 诱导的沉默复合物（RISC）。Drosha 和 Dicer 复合物结构分析的进展使这些分子机器的驱动机制得以阐明。miRNA 的转录、Drosha 和 Dicer 的加工以及 RISC 的加载是 miRNA 生物发生的关键步骤，各种额外的因素促进、支持或抑制这些过程。最近的研究表明，调节因子不仅协调单个 miRNA 加工步骤，而且将 miRNA 生物发生与其他细胞过程联系起来。例如，蛋白质磷酸化将 miRNA 生物发生与各种信号通路联系起来，并且这种修饰通常与疾病相关。此外，并非所有 miRNA 都遵循经典的加工途径，并且最近已经描述了许多非经典的 miRNA 生物发生途径。
