Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis

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-med...

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Main Authors: Matsuyama, Hironori, Suzuki, Hiroshi
Other Authors: Koch Institute for Integrative Cancer Research at MIT
Format: Article
Language:English
Published: MDPI AG 2020
Online Access:https://hdl.handle.net/1721.1/125355
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author Matsuyama, Hironori
Suzuki, Hiroshi
author2 Koch Institute for Integrative Cancer Research at MIT
author_facet Koch Institute for Integrative Cancer Research at MIT
Matsuyama, Hironori
Suzuki, Hiroshi
author_sort Matsuyama, Hironori
collection MIT
description 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.
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spelling mit-1721.1/1253552022-10-02T04:06:56Z Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis Matsuyama, Hironori Suzuki, Hiroshi Koch Institute for Integrative Cancer Research at MIT 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. 2020-05-20T18:13:45Z 2020-05-20T18:13:45Z 2019-12 2019-12 2020-05-19T12:54:12Z Article http://purl.org/eprint/type/JournalArticle 1422-0067 https://hdl.handle.net/1721.1/125355 Matsuyama, Hironori and Hiroshi Suzuki. "Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis." International Journal of Molecular Sciences 21,1 (December 2019): 132 © 2019 The Author(s) en http://dx.doi.org/10.3390/ijms21010132 International Journal of Molecular Sciences Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf MDPI AG MDPI
spellingShingle Matsuyama, Hironori
Suzuki, Hiroshi
Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis
title Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis
title_full Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis
title_fullStr Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis
title_full_unstemmed Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis
title_short Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis
title_sort systems and synthetic microrna biology from biogenesis to disease pathogenesis
url https://hdl.handle.net/1721.1/125355
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