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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981965/ https://www.ncbi.nlm.nih.gov/pubmed/31878193 http://dx.doi.org/10.3390/ijms21010132 |
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author | Matsuyama, Hironori Suzuki, Hiroshi I. |
author_facet | Matsuyama, Hironori Suzuki, Hiroshi I. |
author_sort | Matsuyama, Hironori |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6981965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69819652020-02-07 Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis Matsuyama, Hironori Suzuki, Hiroshi I. Int J Mol Sci Review 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. MDPI 2019-12-24 /pmc/articles/PMC6981965/ /pubmed/31878193 http://dx.doi.org/10.3390/ijms21010132 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Matsuyama, Hironori Suzuki, Hiroshi I. 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 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981965/ https://www.ncbi.nlm.nih.gov/pubmed/31878193 http://dx.doi.org/10.3390/ijms21010132 |
work_keys_str_mv | AT matsuyamahironori systemsandsyntheticmicrornabiologyfrombiogenesistodiseasepathogenesis AT suzukihiroshii systemsandsyntheticmicrornabiologyfrombiogenesistodiseasepathogenesis |