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Regulation of microRNA biogenesis and its crosstalk with other cellular pathways.
Nature Reviews Molecular Cell Biology ( IF 90.2 ) Pub Date : 2019-01-01 , DOI: 10.1038/s41580-018-0059-1
Thomas Treiber Nora Treiber Gunter Meister

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.

中文翻译:

调节 microRNA 生物发生及其与其他细胞途径的相互作用。

MicroRNAs (miRNAs) 是短的非编码 RNAs,通过直接结合靶基因的 mRNAs 来抑制靶基因的表达。miRNA 被转录为前体分子,随后被内切核糖核酸酶 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我们能够阐明驱动这些分子机器的机制。miRNA 的转录、它们通过 Drosha 和 Dicer 的加工以及 RISC 加载是 miRNA 生物发生的关键步骤,并且各种其他因素促进、支持或抑制这些过程。最近的研究表明,调节因子不仅可以协调单个 miRNA 加工步骤,还可以将 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 的生物发生与各种信号通路联系起来,这种修饰通常与疾病有关。此外,并非所有 miRNA 都遵循规范的加工途径,并且最近已经表征了许多非规范的 miRNA 生物发生途径。
更新日期:2019-01-26
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