Why does the m6A writer complex require so many proteins?
Fig 3
Auxiliary proteins may act as rate-limiting factors of the m6A writer complex.
Here we use the term ‘rate-limiting’ to describe the functionally limiting component, based on knockdown correlations rather than direct kinetic measurements. About 50% of m6A remained when METTL3 was reduced to 5%, showing that only a small amount of METTL3 is required to maintain physiological levels of m6A in mRNA. This suggests that METTL3 is not the rate-limiting factor for m6A methylation. By contrast, reducing the level of the auxiliary protein WTAP (to 15%) caused a proportional decrease in m6A (to 15%), indicating a rate-limiting role of WTAP in m6A deposition. The abundance of each protein and its dynamic assembly into the m6A writer complex may regulate sensitivity to METTL3 depletion. Further work is needed to identify the relationships between METTL3 and other auxiliary proteins. Created in BioRender. Jaffrey, S. (2025) https://BioRender.com/alkhfzt.