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.