CHAPTER 9: RNA Demethylation by FTO and ALKBH5
Published:23 Apr 2015
RNA plays a central role in the flow of genetic information in the central dogma. Over 100 structurally distinct post-transcriptional modifications have been identified in RNA, yet little is known about the functions of most of these modifications. N6-methyladenosine (m6A) is one of the most intriguing RNA modifications and is also the most abundant internal modification in mammalian messenger RNA (mRNA). Here we describe the first two RNA m6A demethylases, FTO and ALKBH5, discovered by us. Both belong to the Fe(ii)/2-oxoglutarate-dependent dioxygenases and use an oxidative demethylation mechanism. We review their structures, functions, oxidation mechanisms, as well as biological significance. The emerging field of reversible m6A RNA methylation in biological regulation is also discussed.