Over 150 types of post-transcriptional RNA modifications have been identified in all kingdoms of life. We have discovered two RNA demethylases, FTO and ALKBH5, which catalyze oxidative demethylation of the most prevalent modifications of mammalian messenger RNA (mRNA) and other nuclear RNA, N6-methyladenosine (m6A). These findings indicate that reversible RNA modification could impact biological regulation analogous to the well-known reversible DNA and histone chemical modifications. I will present recent discoveries on m6A-mediated regulation of both transcriptional and post-transcriptional events. We found m6A methylation of chromatin-associated regulatory RNAs (promoter-associated RNAs, enhancer RNAs, and repeat RNAs), or carRNAs. carRNA methylation regulates local chromatin state and downstream transcription. Regulatory pathways and underlying mechanisms will be presented.
