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PARTICLE, a triplex-forming long ncRNA, regulates locus-specific methylation in response to low-dose irradiation.
Cell Rep. 11, 474-485 (2015)
Exposure to low-dose irradiation causes transiently elevated expression of the long ncRNA PARTICLE (gene PARTICLE, promoter of MAT2A-antisense radiation-induced circulating lncRNA). PARTICLE affords both a cytosolic scaffold for the tumor suppressor methionine adenosyltransferase (MAT2A) and a nuclear genetic platform for transcriptional repression. In situ hybridization discloses that PARTICLE and MAT2A associate together following irradiation. Bromouridine tracing and presence in exosomes indicate intercellular transport, and this is supported by ex vivo data from radiotherapy-treated patients. Surface plasmon resonance indicates that PARTICLE forms a DNA-lncRNA triplex upstream of a MAT2A promoter CpG island. We show that PARTICLE represses MAT2A via methylation and demonstrate that the radiation-induced PARTICLE interacts with the transcription-repressive complex proteins G9a and SUZ12 (subunit of PRC2). The interplay of PARTICLE with MAT2A implicates this lncRNA in intercellular communication and as a recruitment platform for gene-silencing machineries through triplex formation in response to irradiation.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Rna-polymerase-ii; Noncoding Rnas; Molecular-mechanisms; Gene-expression; Histone H3; Transcription; Radiation; Cancer; Complexes; Cells
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 11,
Issue: 3,
Pages: 474-485
Publisher
Cell Press
Publishing Place
Cambridge
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Radiation Biology (ISB)