Transcription of Repeats Activates Interferon (TRAIN) Mechanism in Oncology and Aging
“Transcription of Repeats Activates Interferon (TRAIN) Mechanism in Oncology and Aging,” collaboration with Roswell Park Cancer Institute, Tartis Inc., Oncotartis Inc. and TartisAging Inc. (Buffalo, NY, USA).
Expression of interspersed repeats (SINEs) and pericentromeric tandem repeats in the genome of normal mouse cells is blocked by p53 and DNA methylation, either of which is sufficient for transcriptional silencing. Combined p53 inactivation and DNA demethylation through experimental means or natural circumstances (as in tumor cells) lead to unsilencing and massive transcription of these repeat elements, followed by triggering of a suicidal type I interferon (IFN) response. The predicted ability of repeat transcripts to form dsRNA likely mediates the observed IFN induction in cells with unsilenced repeats.