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Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28

miRNAs are small noncoding RNAs capable of regulating gene expression at the post-transcriptional level. A growing body of evidence demonstrated that let-7 family of miRNAs, as one of the highly conserved miRNAs, plays an important role in cell differentiation and development, as well as tumor suppr...

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Detalles Bibliográficos
Autores principales: Shi, Fei, Yu, Wenbao, Wang, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227264/
https://www.ncbi.nlm.nih.gov/pubmed/25338050
http://dx.doi.org/10.3390/ijms151019119
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author Shi, Fei
Yu, Wenbao
Wang, Xia
author_facet Shi, Fei
Yu, Wenbao
Wang, Xia
author_sort Shi, Fei
collection PubMed
description miRNAs are small noncoding RNAs capable of regulating gene expression at the post-transcriptional level. A growing body of evidence demonstrated that let-7 family of miRNAs, as one of the highly conserved miRNAs, plays an important role in cell differentiation and development, as well as tumor suppressor function depending on their levels of expression. To explore the physiological significance of let-7 in regulating cell fate decisions, we present a coarse grained model of let-7 biogenesis network, in which let-7 and its regulator Lin28 inhibit mutually. The dynamics of this minimal network architecture indicates that, as the concentration of Lin28 increases, the system undergoes a transition from monostability to a bistability and then to a one-way switch with increasing strength of positive feedback of let-7, while in the absence of Lin28 inhibition, the system loses bistability. Moreover, the ratio of degradation rates of let-7 and Lin28 is critical for the switching sensitivity and resistance to stimulus fluctuations. These findings may highlight why let-7 is required for normal gene expression in the context of embryonic development and oncogenesis, which will facilitate the development of approaches to exploit this regulatory pathway by manipulating Lin28/let-7 axis for novel treatments of human diseases.
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spelling pubmed-42272642014-11-12 Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28 Shi, Fei Yu, Wenbao Wang, Xia Int J Mol Sci Article miRNAs are small noncoding RNAs capable of regulating gene expression at the post-transcriptional level. A growing body of evidence demonstrated that let-7 family of miRNAs, as one of the highly conserved miRNAs, plays an important role in cell differentiation and development, as well as tumor suppressor function depending on their levels of expression. To explore the physiological significance of let-7 in regulating cell fate decisions, we present a coarse grained model of let-7 biogenesis network, in which let-7 and its regulator Lin28 inhibit mutually. The dynamics of this minimal network architecture indicates that, as the concentration of Lin28 increases, the system undergoes a transition from monostability to a bistability and then to a one-way switch with increasing strength of positive feedback of let-7, while in the absence of Lin28 inhibition, the system loses bistability. Moreover, the ratio of degradation rates of let-7 and Lin28 is critical for the switching sensitivity and resistance to stimulus fluctuations. These findings may highlight why let-7 is required for normal gene expression in the context of embryonic development and oncogenesis, which will facilitate the development of approaches to exploit this regulatory pathway by manipulating Lin28/let-7 axis for novel treatments of human diseases. MDPI 2014-10-21 /pmc/articles/PMC4227264/ /pubmed/25338050 http://dx.doi.org/10.3390/ijms151019119 Text en © 2014 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shi, Fei
Yu, Wenbao
Wang, Xia
Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28
title Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28
title_full Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28
title_fullStr Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28
title_full_unstemmed Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28
title_short Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28
title_sort bistable switch in let-7 mirna biogenesis pathway involving lin28
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227264/
https://www.ncbi.nlm.nih.gov/pubmed/25338050
http://dx.doi.org/10.3390/ijms151019119
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