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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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Autores principales: Matsuyama, Hironori, Suzuki, Hiroshi I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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
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