ALBA proteins facilitate cytoplasmic YTHDF-mediated reading of m6A in Arabidopsis

Abstract

N6-methyladenosine (m6A) 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 m6A 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 m6A sites. These binding sites correspond to pyrimidine-rich elements previously found to be important for m6A binding to ECT2. Accordingly, both the biological functions of ECT2, and its binding to m6A targets in vivo, require ALBA association. Our results introduce the YTHDF-ALBA complex as the functional cytoplasmic m6A-reader in Arabidopsis, and define a molecular foundation for the concept of facilitated m6A reading, which increases the potential for combinatorial control of biological m6A effects.