O'Leary Valerie Bríd, Ovsepian Saak Victor, Carrascosa Laura Garcia, Buske Fabian Andreas, Radulovic Vanja, Niyazi Maximilian, Moertl Simone, Trau Matt, Atkinson Michael John, Anastasov Nataša
Cell Rep. 2015 Apr 21;11(3):474-85. doi: 10.1016/j.celrep.2015.03.043.
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.
暴露于低剂量辐射会导致长链非编码RNA PARTICLE（基因PARTICLE，MAT2A反义辐射诱导循环长链非编码RNA的启动子）的表达瞬时升高。PARTICLE既为肿瘤抑制因子甲硫氨酸腺苷转移酶（MAT2A）提供了一个胞质支架，也为转录抑制提供了一个核遗传平台。原位杂交显示，辐射后PARTICLE和MAT2A会结合在一起。溴尿苷追踪和外泌体中的存在表明其存在细胞间运输，这一点得到了放疗患者的体外数据支持。表面等离子体共振表明，PARTICLE在MAT2A启动子CpG岛上游形成DNA-长链非编码RNA三链体。我们发现PARTICLE通过甲基化抑制MAT2A，并证明辐射诱导的PARTICLE与转录抑制复合物蛋白G9a和SUZ12（PRC2的亚基）相互作用。PARTICLE与MAT2A的相互作用表明，这种长链非编码RNA参与细胞间通讯，并作为一个募集平台，通过响应辐射形成三链体来招募基因沉默机制。
