title: PARTICLE, a Triplex-Forming Long ncRNA, Regulates Locus-Specific Methylation in Response to Low-Dose Irradiation.
abstract: 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.
authors.forename: Valerie Bríd
authors.initials: VB
authors.lastname: O'Leary
authors.forename: Saak Victor
authors.initials: SV
authors.lastname: Ovsepian
authors.forename: Laura Garcia
authors.initials: LG
authors.lastname: Carrascosa
authors.forename: Fabian Andreas
authors.initials: FA
authors.lastname: Buske
authors.forename: Vanja
authors.initials: V
authors.lastname: Radulovic
authors.forename: Maximilian
authors.initials: M
authors.lastname: Niyazi
authors.forename: Simone
authors.initials: S
authors.lastname: Moertl
authors.forename: Matt
authors.initials: M
authors.lastname: Trau
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: Nataša
authors.initials: N
authors.lastname: Anastasov
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000235:genetics / Q000528:radiation effects*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D008716:Methionine Adenosyltransferase / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics*; D011839:Radiation, Ionizing; D000077195:Squamous Cell Carcinoma of Head and Neck; D020349:Surface Plasmon Resonance
chemical_list: D062085:RNA, Long Noncoding; C527161:MAT2A protein, human; D008716:Methionine Adenosyltransferase