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A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells

Telomeres protect chromosome ends from being recognized as double-stranded breaks. Telomeric function is ensured by the shelterin complex in which TRF2 protein is an essential player. The G-rich strand of telomere DNA can fold into G-quadruplex (G4) structure. Small molecules stabilizing G4 structur...

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Autores principales: Gomez, Dennis, Guédin, Aurore, Mergny, Jean-Louis, Salles, Bernard, Riou, Jean-François, Teulade-Fichou, Marie-Paule, Calsou, Patrick
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978344/
https://www.ncbi.nlm.nih.gov/pubmed/20571083
http://dx.doi.org/10.1093/nar/gkq563
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author Gomez, Dennis
Guédin, Aurore
Mergny, Jean-Louis
Salles, Bernard
Riou, Jean-François
Teulade-Fichou, Marie-Paule
Calsou, Patrick
author_facet Gomez, Dennis
Guédin, Aurore
Mergny, Jean-Louis
Salles, Bernard
Riou, Jean-François
Teulade-Fichou, Marie-Paule
Calsou, Patrick
author_sort Gomez, Dennis
collection PubMed
description Telomeres protect chromosome ends from being recognized as double-stranded breaks. Telomeric function is ensured by the shelterin complex in which TRF2 protein is an essential player. The G-rich strand of telomere DNA can fold into G-quadruplex (G4) structure. Small molecules stabilizing G4 structures, named G4 ligands, have been shown to alter telomeric functions in human cells. In this study, we show that a guanine-rich RNA sequence located in the 5′-UTR region of the TRF2 mRNA (hereafter 91TRF2G) is capable of forming a stable quadruplex that causes a 2.8-fold decrease in the translation of a reporter gene in human cells, as compared to a mutant 5′-UTR unable to fold into G4. We also demonstrate that several highly selective G4 ligands, the pyridine dicarboxamide derivative 360A and bisquinolinium compounds Phen-DC(3) and Phen-DC(6), are able to bind the 91TRF2G:RNA sequence and to modulate TRF2 protein translation in vitro. Since the naturally occurring 5′-UTR TRF2:RNA G4 element was used here, which is conserved in several vertebrate orthologs, the present data substantiate a potential translational mechanism mediated by a G4 RNA motif for the downregulation of TRF2 expression.
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spelling pubmed-29783442010-11-12 A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells Gomez, Dennis Guédin, Aurore Mergny, Jean-Louis Salles, Bernard Riou, Jean-François Teulade-Fichou, Marie-Paule Calsou, Patrick Nucleic Acids Res RNA Telomeres protect chromosome ends from being recognized as double-stranded breaks. Telomeric function is ensured by the shelterin complex in which TRF2 protein is an essential player. The G-rich strand of telomere DNA can fold into G-quadruplex (G4) structure. Small molecules stabilizing G4 structures, named G4 ligands, have been shown to alter telomeric functions in human cells. In this study, we show that a guanine-rich RNA sequence located in the 5′-UTR region of the TRF2 mRNA (hereafter 91TRF2G) is capable of forming a stable quadruplex that causes a 2.8-fold decrease in the translation of a reporter gene in human cells, as compared to a mutant 5′-UTR unable to fold into G4. We also demonstrate that several highly selective G4 ligands, the pyridine dicarboxamide derivative 360A and bisquinolinium compounds Phen-DC(3) and Phen-DC(6), are able to bind the 91TRF2G:RNA sequence and to modulate TRF2 protein translation in vitro. Since the naturally occurring 5′-UTR TRF2:RNA G4 element was used here, which is conserved in several vertebrate orthologs, the present data substantiate a potential translational mechanism mediated by a G4 RNA motif for the downregulation of TRF2 expression. Oxford University Press 2010-11 2010-06-22 /pmc/articles/PMC2978344/ /pubmed/20571083 http://dx.doi.org/10.1093/nar/gkq563 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Gomez, Dennis
Guédin, Aurore
Mergny, Jean-Louis
Salles, Bernard
Riou, Jean-François
Teulade-Fichou, Marie-Paule
Calsou, Patrick
A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells
title A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells
title_full A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells
title_fullStr A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells
title_full_unstemmed A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells
title_short A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells
title_sort g-quadruplex structure within the 5′-utr of trf2 mrna represses translation in human cells
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978344/
https://www.ncbi.nlm.nih.gov/pubmed/20571083
http://dx.doi.org/10.1093/nar/gkq563
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