The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation.

The nuclear envelope can regulate gene expression through its interaction with chromatin and by the sequestration of specific transcription factors. In this study, we show that such regulation can be achieved via microRNA regulation. We identify a set of miRNAs that are dysregulated in the absence o...

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Main Authors: Malhas, A, Saunders, N, Vaux, D
Format: Journal article
Language:English
Published: 2010
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author Malhas, A
Saunders, N
Vaux, D
author_facet Malhas, A
Saunders, N
Vaux, D
author_sort Malhas, A
collection OXFORD
description The nuclear envelope can regulate gene expression through its interaction with chromatin and by the sequestration of specific transcription factors. In this study, we show that such regulation can be achieved via microRNA regulation. We identify a set of miRNAs that are dysregulated in the absence of a fully functional nuclear lamina. We then focus on miRNA-31 and experimentally confirm its targets. The target set identified is significantly enriched in genes involved in controlling progress through the cell cycle such as Cdkn2a. Normalizing miRNA-31 levels, either using a specific inhibitor or by restoration of the nuclear lamina, also normalizes cell cycle distribution and cell proliferation rates. We show that the 3'UtR of p16(Ink4a)/p19(Arf) has a functional miRNA-31 binding site which contributes to the observed regulation of cell cycle progression. Our findings are the first demonstration that the nuclear envelope can control gene expression by regulating specific miRNA levels, and that miRNA-31 is involved in the regulation of cell proliferation and progress through the cell cycle at least in part by regulating the levels of p16(Ink4a)/p19(Arf).
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spelling oxford-uuid:77d2c561-7222-4421-a9e6-7caf4fed579c2022-03-26T20:26:42ZThe nuclear envelope can control gene expression and cell cycle progression via miRNA regulation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:77d2c561-7222-4421-a9e6-7caf4fed579cEnglishSymplectic Elements at Oxford2010Malhas, ASaunders, NVaux, DThe nuclear envelope can regulate gene expression through its interaction with chromatin and by the sequestration of specific transcription factors. In this study, we show that such regulation can be achieved via microRNA regulation. We identify a set of miRNAs that are dysregulated in the absence of a fully functional nuclear lamina. We then focus on miRNA-31 and experimentally confirm its targets. The target set identified is significantly enriched in genes involved in controlling progress through the cell cycle such as Cdkn2a. Normalizing miRNA-31 levels, either using a specific inhibitor or by restoration of the nuclear lamina, also normalizes cell cycle distribution and cell proliferation rates. We show that the 3'UtR of p16(Ink4a)/p19(Arf) has a functional miRNA-31 binding site which contributes to the observed regulation of cell cycle progression. Our findings are the first demonstration that the nuclear envelope can control gene expression by regulating specific miRNA levels, and that miRNA-31 is involved in the regulation of cell proliferation and progress through the cell cycle at least in part by regulating the levels of p16(Ink4a)/p19(Arf).
spellingShingle Malhas, A
Saunders, N
Vaux, D
The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation.
title The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation.
title_full The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation.
title_fullStr The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation.
title_full_unstemmed The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation.
title_short The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation.
title_sort nuclear envelope can control gene expression and cell cycle progression via mirna regulation
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AT saundersn thenuclearenvelopecancontrolgeneexpressionandcellcycleprogressionviamirnaregulation
AT vauxd thenuclearenvelopecancontrolgeneexpressionandcellcycleprogressionviamirnaregulation
AT malhasa nuclearenvelopecancontrolgeneexpressionandcellcycleprogressionviamirnaregulation
AT saundersn nuclearenvelopecancontrolgeneexpressionandcellcycleprogressionviamirnaregulation
AT vauxd nuclearenvelopecancontrolgeneexpressionandcellcycleprogressionviamirnaregulation