Topic: RNA m6A landscape reveals vulnerability of cancer cells to RNA stability manipulation
Speaker: Associate Professor CHEN Kaifu, Department of Pediatrics, Harvard Medical School (HMS)
Date and time: 10:00–11:00, October 20
Venue: Auditorium, Y Building
Abstract:
Cancer genes were known to display unique epigenetic features on chromatin of benign cells. Investigations into these features are making it increasingly clear that cancer genes differ from other genes regarding the mechanisms regulating their transcription. More recently, we found RNAs of tumor suppressor genes tended to decay fast in multiple benign cell types when compared with other RNAs. Consistent with a negative effect of m6A modification on RNA stability, we observed preferential deposition of m6A on tumor suppressor RNAs. Due to increased transcription frequency, the fast RNA decay of tumor suppressors leads to a quick expression turnover but not a low expression level. The abundant m6A and fast decay of tumor suppressor RNAs both tended to be further enhanced in prostate cancer cells relative to benign prostate epithelial cells. This enhancement correlated with a down regulation of tumor suppressor expression. Further, knockdown of m6A methyltransferase METTL3 and reader protein YTHDF2 in prostate cancer cells posed stronger effect on tumor suppressor RNAs than on other RNAs. These results indicated a strong expression maneuverability of tumor suppressors mediated by abundant m6A modification on RNAs.