ALBA Proteins Facilitate Cytoplasmic YTHDF-mediated Reading of M6A in Arabidopsis
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N6-methyladenosine (mA) exerts many of its regulatory effects on eukaryotic mRNAs by recruiting cytoplasmic YT521-B homology-domain family (YTHDF) proteins. Here, we show that in Arabidopsis thaliana, the interaction between mA and the major YTHDF protein ECT2 also involves the mRNA-binding ALBA protein family. ALBA and YTHDF proteins physically associate via a deeply conserved short linear motif in the intrinsically disordered region of YTHDF proteins and their mRNA target sets overlap, with ALBA4 binding sites being juxtaposed to mA sites. These binding sites correspond to pyrimidine-rich elements previously found to be important for mA binding to ECT2. Accordingly, both the biological functions of ECT2, and its binding to mA targets in vivo, require ALBA association. Our results introduce the YTHDF-ALBA complex as the functional cytoplasmic mA-reader in Arabidopsis, and define a molecular foundation for the concept of facilitated mA reading, which increases the potential for combinatorial control of biological mA effects.