PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome
| Autor: | Laura G. Carrascosa, Wolfgang Heidenreich, Michael J. Atkinson, Sarah Hain, Matt Trau, Valerie B. O'Leary, Jan Smida, Fabian A. Buske, Doris Maugg, Soile Tapio, Saak V. Ovsepian, James Kerr, Omid Azimzadeh |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
WWOX Transcription Genetic Cell Survival MAP Kinase Signaling System Science Locus (genetics) Genome Article WW domain Mice 03 medical and health sciences Transcription (biology) Cell Line Tumor Animals Humans RNA Small Interfering Promoter Regions Genetic Gene Regulation of gene expression Binding Sites Multidisciplinary biology Genome Human Tumor Suppressor Proteins Epistasis Genetic Molecular biology 030104 developmental biology Gene Expression Regulation WW Domain-Containing Oxidoreductase Genetic Loci biology.protein Nucleic Acid Conformation Medicine RNA Interference RNA Long Noncoding Human genome Disease Susceptibility Chromosomes Human Pair 16 Protein Binding |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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