Structural and Dynamic Insights into Redundant Function of YTHDF Proteins

Three YTH-domain family proteins (YTHDF1, YTHDF2, and YTHDF3) recognize the N6-methyladenosine (m6A) modification of mRNA in cells. However, the redundancy of their cellular functions has been disputed. We investigate their interactions with m6A-containing RNA using X-ray crystallography and molecular dynamics (MD). The new X-ray structures and MD simulations show that the three proteins share identical interactions with the m6A-containing RNA and have similar intrinsic plasticity, thus evidencing the redundant roles of the three proteins in cellular functions.