Laboratorio di Biologia Molecolare e Cellulare, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", Università di Pavia Pavia, Italy.
Front Oncol. 2013 May 10;3:115. doi: 10.3389/fonc.2013.00115. eCollection 2013.
Mammalian telomeres are transcribed into long non-coding telomeric repeat-containing RNA (TERRA) molecules that seem to play a role in the maintenance of telomere stability. In human cells, CpG-island promoters drive TERRA transcription and are regulated by methylation. It was suggested that the amount of TERRA may be related to telomere length. To test this hypothesis we measured telomere length and TERRA levels in single clones isolated from five human cell lines: HeLa (cervical carcinoma), BRC-230 (breast cancer), AKG and GK2 (gastric cancers), and GM847 (SV40 immortalized skin fibroblasts). However, these two parameters did not correlate with each other. Moreover, cell survival to γ-rays did not show a significant variation among the clones, suggesting that, in this cellular system, the intra-population variability in telomere length and TERRA levels does not influence sensitivity to ionizing radiation. This conclusion was supported by the observation that in a cell line in which telomeres were greatly elongated by the ectopic expression of telomerase, TERRA expression levels and radiation sensitivity were similar to the parental HeLa cell line.
哺乳动物端粒被转录为长的非编码端粒重复 RNA(TERRA)分子,这些 RNA 似乎在维持端粒稳定性方面发挥作用。在人类细胞中,CpG 岛启动子驱动 TERRA 转录,并受甲基化调控。有人提出,TERRA 的数量可能与端粒长度有关。为了验证这一假设,我们测量了从 5 个人类细胞系(宫颈癌细胞系 HeLa、乳腺癌细胞系 BRC-230、胃癌细胞系 AKG 和 GK2 以及 SV40 永生化皮肤成纤维细胞系 GM847)中分离的单个克隆中端粒长度和 TERRA 水平。然而,这两个参数之间没有相关性。此外,克隆对 γ 射线的存活能力没有显示出明显的差异,这表明在这个细胞系统中,端粒长度和 TERRA 水平的种群内变异性不会影响对电离辐射的敏感性。这一结论得到了以下观察结果的支持:在一个通过端粒酶的异位表达使端粒大大延长的细胞系中,TERRA 表达水平和辐射敏感性与亲本 HeLa 细胞系相似。