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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MDPI AG
2020
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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. |
first_indexed | 2024-09-23T15:47:17Z |
format | Article |
id | mit-1721.1/125355 |
institution | Massachusetts Institute of Technology |
language | English |
last_indexed | 2024-09-23T15:47:17Z |
publishDate | 2020 |
publisher | MDPI AG |
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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 |
work_keys_str_mv | AT matsuyamahironori systemsandsyntheticmicrornabiologyfrombiogenesistodiseasepathogenesis AT suzukihiroshi systemsandsyntheticmicrornabiologyfrombiogenesistodiseasepathogenesis |