Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis

被引：201

作者：

Matsuyama, Hironori ^{[1
]}

Suzuki, Hiroshi I. ^{[2
]}

机构：

[1] Otsuka Pharmaceut Co Ltd, Fujii Mem Res Inst, 1-11-1 Karasaki, Otsu, Shiga 5200106, Japan

[2] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 01期

关键词：

microRNA; RNAi; Drosha; Argonaute; biogenesis; super-enhancer; disease pathogenesis; synthetic biology; ANAPLASTIC LYMPHOMA KINASE; RNA-BINDING PROTEINS; HUMAN ARGONAUTE PROTEINS; HEPATOCELLULAR-CARCINOMA; STAT3; ACTIVATION; SUPER-ENHANCERS; SEED REGION; NPM-ALK; STAT3-MEDIATED ACTIVATION; TUMOR-SUPPRESSOR;

D O I：

10.3390/ijms21010132

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves multiple steps, including the transcription of primary miRNAs (pri-miRNAs), nuclear Drosha-mediated processing, cytoplasmic Dicer-mediated processing, and loading onto Argonaute (Ago) proteins. Further, miRNAs control diverse biological and pathological processes via the silencing of target mRNAs. This review summarizes recent findings regarding the quantitative aspects of miRNA homeostasis, including Drosha-mediated pri-miRNA processing, Ago-mediated asymmetric miRNA strand selection, and modifications of miRNA pathway components, as well as the roles of RNA modifications (epitranscriptomics), epigenetics, transcription factor circuits, and super-enhancers in miRNA regulation. These recent advances have facilitated a system-level understanding of miRNA networks, as well as the improvement of RNAi performance for both gene-specific targeting and genome-wide screening. The comprehensive understanding and modeling of miRNA biogenesis and function have been applied to the design of synthetic gene circuits. In addition, the relationships between miRNA genes and super-enhancers provide the molecular basis for the highly biased cell type-specific expression patterns of miRNAs and the evolution of miRNA-target connections, while highlighting the importance of alterations of super-enhancer-associated miRNAs in a variety of human diseases.

引用

页数：23

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