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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| Format: | Article |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07295-5 |
| _version_ | 1818422037329215488 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T13:19:53Z |
| format | Article |
| id | doaj.art-2868e0c67157411196e1e948c7882360 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:19:53Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2868e0c67157411196e1e948c78823602022-12-21T22:59:57ZengNature PortfolioScientific Reports2045-23222017-08-017111310.1038/s41598-017-07295-5PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genomeValerie Bríd O’Leary0Jan Smida1Fabian Andreas Buske2Laura Garcia Carrascosa3Omid Azimzadeh4Doris Maugg5Sarah Hain6Soile Tapio7Wolfgang Heidenreich8James Kerr9Matt Trau10Saak Victor Ovsepian11Michael John Atkinson12Institute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental HealthInstitute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental HealthKinghorn Cancer Centre, Garvan Institute of Medical ResearchCentre for Personalized Nanomedicine, Australian Institute for Bio-engineering and Nanotechnology, The University of QueenslandInstitute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental HealthInstitute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental HealthInstitute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental HealthInstitute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental HealthInstitute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental HealthCentre for Personalized Nanomedicine, Australian Institute for Bio-engineering and Nanotechnology, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandInstitute of Biological and Medical Imaging, Helmholtz Zentrum Munich - German Research Center for Environmental HealthInstitute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental HealthAbstract 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.https://doi.org/10.1038/s41598-017-07295-5 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-07295-5 |
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