Figure 1. Formation, removal, and recognition of m⁶A.

METTL3/METTL14 were identified as core components of an N⁶-methyladenosine methyltransferase complex. Both form a heterodimer catalyzing m⁶A formation. WTAP has been identified as a METTL3- and METTL14-interacting protein. The presence of WTAP does not alter METTL3/METTL14 methyltransferase activity in vitro, but WTAP has a critical role in m⁶A formation in vivo through an unknown mechanism. Other METTL3/METTL14-interacting proteins have been identified, but their activities remain to be determined. Two Alkb family members, FTO and ALKBH5, reportedly serve as m⁶A demethylases and remove m⁶A in an oxidative manner, although additional unknown m⁶A demethylases may also serve this function. Several m⁶A binding proteins are reported, including multiple YTH family members (YTHDF1–3 and YTHDC1), heterogeneous ribonucleoprotein HNRNPA2B1, and eIF3.