Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions

Abstract Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids seco...

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Autores principales:	Rosalba Perrone, Enrico Lavezzo, Erika Riello, Riccardo Manganelli, Giorgio Palù, Stefano Toppo, Roberta Provvedi, Sara N. Richter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83fdf0d3a1ff4372951f0ab8d77f8fdc
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spelling	oai:doaj.org-article:83fdf0d3a1ff4372951f0ab8d77f8fdc2021-12-02T11:40:15ZMapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions10.1038/s41598-017-05867-z2045-2322https://doaj.org/article/83fdf0d3a1ff4372951f0ab8d77f8fdc2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05867-zhttps://doaj.org/toc/2045-2322Abstract Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites. We found that the most stable G-quadruplexes were in the promoter region of genes belonging to definite functional categories. Actual G-quadruplex folding of four selected sequences was assessed by biophysical and biomolecular techniques: all molecules formed stable G-quadruplexes, which were further stabilized by two G-quadruplex ligands. These compounds inhibited Mycobacterium tuberculosis growth with minimal inhibitory concentrations in the low micromolar range. These data support formation of Mycobacterium tuberculosis G-quadruplexes in vivo and their potential regulation of gene transcription, and prompt the use of G4 ligands to develop original antitubercular agents.Rosalba PerroneEnrico LavezzoErika RielloRiccardo ManganelliGiorgio PalùStefano ToppoRoberta ProvvediSara N. RichterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rosalba Perrone Enrico Lavezzo Erika Riello Riccardo Manganelli Giorgio Palù Stefano Toppo Roberta Provvedi Sara N. Richter Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions
description	Abstract Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites. We found that the most stable G-quadruplexes were in the promoter region of genes belonging to definite functional categories. Actual G-quadruplex folding of four selected sequences was assessed by biophysical and biomolecular techniques: all molecules formed stable G-quadruplexes, which were further stabilized by two G-quadruplex ligands. These compounds inhibited Mycobacterium tuberculosis growth with minimal inhibitory concentrations in the low micromolar range. These data support formation of Mycobacterium tuberculosis G-quadruplexes in vivo and their potential regulation of gene transcription, and prompt the use of G4 ligands to develop original antitubercular agents.
format	article
author	Rosalba Perrone Enrico Lavezzo Erika Riello Riccardo Manganelli Giorgio Palù Stefano Toppo Roberta Provvedi Sara N. Richter
author_facet	Rosalba Perrone Enrico Lavezzo Erika Riello Riccardo Manganelli Giorgio Palù Stefano Toppo Roberta Provvedi Sara N. Richter
author_sort	Rosalba Perrone
title	Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions
title_short	Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions
title_full	Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions
title_fullStr	Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions
title_full_unstemmed	Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions
title_sort	mapping and characterization of g-quadruplexes in mycobacterium tuberculosis gene promoter regions
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/83fdf0d3a1ff4372951f0ab8d77f8fdc
work_keys_str_mv	AT rosalbaperrone mappingandcharacterizationofgquadruplexesinmycobacteriumtuberculosisgenepromoterregions AT enricolavezzo mappingandcharacterizationofgquadruplexesinmycobacteriumtuberculosisgenepromoterregions AT erikariello mappingandcharacterizationofgquadruplexesinmycobacteriumtuberculosisgenepromoterregions AT riccardomanganelli mappingandcharacterizationofgquadruplexesinmycobacteriumtuberculosisgenepromoterregions AT giorgiopalu mappingandcharacterizationofgquadruplexesinmycobacteriumtuberculosisgenepromoterregions AT stefanotoppo mappingandcharacterizationofgquadruplexesinmycobacteriumtuberculosisgenepromoterregions AT robertaprovvedi mappingandcharacterizationofgquadruplexesinmycobacteriumtuberculosisgenepromoterregions AT saranrichter mappingandcharacterizationofgquadruplexesinmycobacteriumtuberculosisgenepromoterregions
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Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions

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