Modomics - A Database of RNA Modifications

Published on None in volume None.

PubMed ID: 36167981

DOI: 10.1038/s41422-022-00725-8


N 6 -methyladenosine (m 6 A) is the most abundant ribonucleotide modification among eukaryotic messenger RNAs. The m 6 A "writer" consists of the catalytic subunit m 6 A-METTL complex (MAC) and the regulatory subunit m 6 A-METTL-associated complex (MACOM), the latter being essential for enzymatic activity. Here, we report the cryo-electron microscopy (cryo-EM) structures of MACOM at a 3.0-Å resolution, uncovering that WTAP and VIRMA form the core structure of MACOM and that ZC3H13 stretches the conformation by binding VIRMA. Furthermore, the 4.4-Å resolution cryo-EM map of the MACOM-MAC complex, combined with crosslinking mass spectrometry and GST pull-down analysis, elucidates a plausible model of the m 6 A writer complex, in which MACOM binds to MAC mainly through WTAP and METTL3 interactions. In combination with in vitro RNA substrate binding and m 6 A methyltransferase activity assays, our results illustrate the molecular basis of how MACOM assembles and interacts with MAC to form an active m 6 A writer complex.