Discovery of Small Molecules that Activate RNA Methylation through Cooperative Binding to the METTL3-14-WTAP Complex Active Site

• DOI: 10.1016/j.celrep.2019.02.100
• Publication Date: 2019-03-26T14:43:34Z
• Authors: Simona Selberg; Daria Blokhina; Maria Aatonen; Pertti Koivisto; Antti Siltanen; Eero Mervaala; Esko Kankuri; Mati Karelson
• Keywords: N6-Methyladenosine; RNA methylation

Chemical modifications of RNA provide an additional, epitranscriptomic, level control over cellular functions. N-6-methylated adenosines (m6As) are found in several types RNA, and their amounts regulated by methyltransferases demethylases. One the most important enzymes catalyzing generation m6A on mRNA is trimer N-6-methyltransferase METTL3-14-WTAP complex. Its activity has been linked to such critical biological processes as cell differentiation, proliferation, death.We used silico-based discovery identify small-molecule ligands that bind determined experimentally binding affinity kinetics, well effect enzymatic function. We show these serve activators