Increased amounts and stability of telomeric repeat-containing RNA (TERRA) following DNA damage induced by etoposide


Autoři: Bong-Kyeong Oh aff001;  Yoojung Choi aff002;  Jaeman Bae aff003;  Won Moo Lee aff003;  Jeong-Kyu Hoh aff003;  Joong Sub Choi aff001
Působiště autorů: Institute for the Integration of Medicine and Innovative Technology, Hanyang University College of Medicine, Seoul, Korea aff001;  Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, Korea aff002;  Department of Obstetrics and Gynecology, Hanyang University College of Medicine, Seoul, Korea aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225302

Souhrn

Telomeric repeat-containing RNAs (TERRAs) are long noncoding RNAs transcribed from subtelomeres toward telomeric repeat tracts, which have been implicated in telomere protection and heterochromatin formation. Genotoxic stress leads to upregulation of TERRAs. However, the mechanism of DNA damage-mediated TERRA induction remains elusive. Here, we treated HeLa cells with etoposide, a DNA double-strand break-generating agent, for various times and monitored the levels of TERRAs. Etoposide treatment led to a gradual time-dependent increase in TERRAs. Etoposide-mediated induction was evident in many TERRAs arising from various chromosome loci, including 20q and XpYp. Chromatin immunoprecipitation assays revealed no significant changes in the occupancy of RNA polymerase II at telomeres upon etoposide treatment. Interestingly, TERRAs arising from 20q, XpYp, 10q, and 13q degraded at slower rates in cells treated with etoposide, while degradation rates of TERRAs from many loci tested were nearly identical in both etoposide- and mock-treated cells. Telomere damage occurred from early time points of etoposide treatment, but telomere lengths and abundance of telomeric repeat-binding factor 2 (TRF2) at telomeres remained unchanged. In summary, etoposide treatment led to telomere damage and TERRA accumulation, but telomere lengths and TRF2-mediated telomere integrity were maintained. Etoposide-mediated TERRA accumulation could be attributed partly to RNA stabilization. These findings may provide insight into the post-transcriptional regulation of TERRAs in response to DNA damage.

Klíčová slova:

DNA damage – Genetic loci – HeLa cells – Probe hybridization – Ribosomal RNA – Telomere length – Telomeres – Cell hybridization


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