PARTICLE - a triplex-forming long ncRNA regulates locus specific methylation in response to low dose irradiation

Exposure to low dose irradiation causes transiently elevated expression of a long ncRNA PARTICLE (Gene PARTICL- 'Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA). PARTICLE affords both a cytosolic scaffold for th e tumor suppressor methionine adenosyltransferase (MAT2A) and a n...

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Published in:	Cell reports (Cambridge) Vol. 11; no. 3; pp. 474 - 485
Main Authors:	O'Leary, Valerie Bríd, Ovsepian, Saak Victor, Carrascosa, Laura Garcia, Buske, Fabian Andreas, Radulovic, Vanja, Niyazi, Maximilian, Moertl, Simone, Trau, Matt, Atkinson, MichaelJohn, Anastasov, Nataša
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 21-04-2015 Elsevier
Subjects:	Carcinoma, Squamous Cell - radiotherapy Cell Line Chromatin Immunoprecipitation DNA Methylation - genetics DNA Methylation - radiation effects Electrophoretic Mobility Shift Assay Gene Expression Regulation - radiation effects Head and Neck Neoplasms - radiotherapy Humans Immunoblotting In Situ Hybridization Methionine Adenosyltransferase - biosynthesis Methionine Adenosyltransferase - genetics Oligonucleotide Array Sequence Analysis Radiation, Ionizing RNA, Long Noncoding - biosynthesis RNA, Long Noncoding - genetics Squamous Cell Carcinoma of Head and Neck Surface Plasmon Resonance
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Summary:	Exposure to low dose irradiation causes transiently elevated expression of a long ncRNA PARTICLE (Gene PARTICL- 'Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA). PARTICLE affords both a cytosolic scaffold for th e tumor suppressor methionine adenosyltransferase (MAT2A) and a nuclear genetic platform for transcriptional repression. In situ hybridisation discloses that PARTICLE-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 lncRNA 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 as well as a recruitment platform for gene silencing machineries through triplex formation in response to irradiation. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2015.03.043