PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome

Abstract The long non-coding RNA PARTICLE (Gene PARTICL- ‘Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA) partakes in triple helix (triplex) formation, is transiently elevated following low dose irradiation and regulates transcription of its neighbouring gene - Methionine adenosylt...

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Autores principales:	Valerie Bríd O’Leary, Jan Smida, Fabian Andreas Buske, Laura Garcia Carrascosa, Omid Azimzadeh, Doris Maugg, Sarah Hain, Soile Tapio, Wolfgang Heidenreich, James Kerr, Matt Trau, Saak Victor Ovsepian, Michael John Atkinson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2868e0c67157411196e1e948c7882360
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spelling	oai:doaj.org-article:2868e0c67157411196e1e948c78823602021-12-02T11:52:58ZPARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome10.1038/s41598-017-07295-52045-2322https://doaj.org/article/2868e0c67157411196e1e948c78823602017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07295-5https://doaj.org/toc/2045-2322Abstract The long non-coding RNA PARTICLE (Gene PARTICL- ‘Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA) partakes in triple helix (triplex) formation, is transiently elevated following low dose irradiation and regulates transcription of its neighbouring gene - Methionine adenosyltransferase 2A. It now emerges that PARTICLE triplex sites are predicted in many different genes across all human chromosomes. In silico analysis identified additional regions for PARTICLE triplexes at >1600 genomic locations. Multiple PARTICLE triplexes are clustered predominantly within the human and mouse tumor suppressor WW Domain Containing Oxidoreductase (WWOX) gene. Surface plasmon resonance diffraction and electrophoretic mobility shift assays were consistent with PARTICLE triplex formation within human WWOX with high resolution imaging demonstrating its enrichment at this locus on chromosome 16. PARTICLE knockdown and over-expression resulted in inverse changes in WWOX transcripts levels with siRNA interference eliminating PARTICLEs elevated transcription to irradiation. The evidence for a second functional site of PARTICLE triplex formation at WWOX suggests that PARTICLE may form triplex-mediated interactions at multiple positions in the human genome including remote loci. These findings provide a mechanistic explanation for the ability of lncRNAs to regulate the expression of numerous genes distributed across the genome.Valerie Bríd O’LearyJan SmidaFabian Andreas BuskeLaura Garcia CarrascosaOmid AzimzadehDoris MauggSarah HainSoile TapioWolfgang HeidenreichJames KerrMatt TrauSaak Victor OvsepianMichael John AtkinsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Valerie Bríd O’Leary Jan Smida Fabian Andreas Buske Laura Garcia Carrascosa Omid Azimzadeh Doris Maugg Sarah Hain Soile Tapio Wolfgang Heidenreich James Kerr Matt Trau Saak Victor Ovsepian Michael John Atkinson PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome
description	Abstract The long non-coding RNA PARTICLE (Gene PARTICL- ‘Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA) partakes in triple helix (triplex) formation, is transiently elevated following low dose irradiation and regulates transcription of its neighbouring gene - Methionine adenosyltransferase 2A. It now emerges that PARTICLE triplex sites are predicted in many different genes across all human chromosomes. In silico analysis identified additional regions for PARTICLE triplexes at >1600 genomic locations. Multiple PARTICLE triplexes are clustered predominantly within the human and mouse tumor suppressor WW Domain Containing Oxidoreductase (WWOX) gene. Surface plasmon resonance diffraction and electrophoretic mobility shift assays were consistent with PARTICLE triplex formation within human WWOX with high resolution imaging demonstrating its enrichment at this locus on chromosome 16. PARTICLE knockdown and over-expression resulted in inverse changes in WWOX transcripts levels with siRNA interference eliminating PARTICLEs elevated transcription to irradiation. The evidence for a second functional site of PARTICLE triplex formation at WWOX suggests that PARTICLE may form triplex-mediated interactions at multiple positions in the human genome including remote loci. These findings provide a mechanistic explanation for the ability of lncRNAs to regulate the expression of numerous genes distributed across the genome.
format	article
author	Valerie Bríd O’Leary Jan Smida Fabian Andreas Buske Laura Garcia Carrascosa Omid Azimzadeh Doris Maugg Sarah Hain Soile Tapio Wolfgang Heidenreich James Kerr Matt Trau Saak Victor Ovsepian Michael John Atkinson
author_facet	Valerie Bríd O’Leary Jan Smida Fabian Andreas Buske Laura Garcia Carrascosa Omid Azimzadeh Doris Maugg Sarah Hain Soile Tapio Wolfgang Heidenreich James Kerr Matt Trau Saak Victor Ovsepian Michael John Atkinson
author_sort	Valerie Bríd O’Leary
title	PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome
title_short	PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome
title_full	PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome
title_fullStr	PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome
title_full_unstemmed	PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome
title_sort	particle triplexes cluster in the tumor suppressor wwox and may extend throughout the human genome
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2868e0c67157411196e1e948c7882360
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PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome

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