Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.

MicroRNAs are endogenous 23-25 nt RNAs that play important gene-regulatory roles in animals and plants. Recently, miR369-3 was found to upregulate translation of TNFα mRNA in quiescent (G0) mammalian cell lines. Knock down and immunofluorescence experiments suggest that microRNA-protein complexes (w...

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Main Authors: Wei Ye, Fang Qin, Jian Zhang, Ray Luo, Hai-Feng Chen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3428290?pdf=render
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spelling doaj-200f8c9fae784a53830e0502ea1a46e32020-11-25T02:15:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4378810.1371/journal.pone.0043788Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.Wei YeFang QinJian ZhangRay LuoHai-Feng ChenMicroRNAs are endogenous 23-25 nt RNAs that play important gene-regulatory roles in animals and plants. Recently, miR369-3 was found to upregulate translation of TNFα mRNA in quiescent (G0) mammalian cell lines. Knock down and immunofluorescence experiments suggest that microRNA-protein complexes (with FXR1 and AGO2) are necessary for the translation upregulation. However the molecular mechanism of microRNA translation activation is poorly understood. In this study we constructed the microRNA-mRNA-AGO2-FXR1 quadruple complex by bioinformatics and molecular modeling, followed with all atom molecular dynamics simulations in explicit solvent to investigate the interaction mechanisms for the complex. A combined analysis of experimental and computational data suggests that AGO2-FXR1 complex relocalize microRNA:mRNA duplex to polysomes in G0. The two strands of dsRNA are then separated upon binding of AGO2 and FXR1. Finally, polysomes may improve the translation efficiency of mRNA. The mutation research confirms the stability of microRNA-mRNA-FXR1 and illustrates importance of key residue of Ile304. This possible mechanism can shed more light on the microRNA-dependent upregulation of translation.http://europepmc.org/articles/PMC3428290?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Wei Ye
Fang Qin
Jian Zhang
Ray Luo
Hai-Feng Chen
spellingShingle Wei Ye
Fang Qin
Jian Zhang
Ray Luo
Hai-Feng Chen
Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.
PLoS ONE
author_facet Wei Ye
Fang Qin
Jian Zhang
Ray Luo
Hai-Feng Chen
author_sort Wei Ye
title Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.
title_short Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.
title_full Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.
title_fullStr Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.
title_full_unstemmed Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.
title_sort atomistic mechanism of microrna translation upregulation via molecular dynamics simulations.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description MicroRNAs are endogenous 23-25 nt RNAs that play important gene-regulatory roles in animals and plants. Recently, miR369-3 was found to upregulate translation of TNFα mRNA in quiescent (G0) mammalian cell lines. Knock down and immunofluorescence experiments suggest that microRNA-protein complexes (with FXR1 and AGO2) are necessary for the translation upregulation. However the molecular mechanism of microRNA translation activation is poorly understood. In this study we constructed the microRNA-mRNA-AGO2-FXR1 quadruple complex by bioinformatics and molecular modeling, followed with all atom molecular dynamics simulations in explicit solvent to investigate the interaction mechanisms for the complex. A combined analysis of experimental and computational data suggests that AGO2-FXR1 complex relocalize microRNA:mRNA duplex to polysomes in G0. The two strands of dsRNA are then separated upon binding of AGO2 and FXR1. Finally, polysomes may improve the translation efficiency of mRNA. The mutation research confirms the stability of microRNA-mRNA-FXR1 and illustrates importance of key residue of Ile304. This possible mechanism can shed more light on the microRNA-dependent upregulation of translation.
url http://europepmc.org/articles/PMC3428290?pdf=render
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