RNA-binding proteins provide specificity to the PAN2-PAN3 mRNA deadenylation complex

Cytoplasmic shortening of mRNA poly(A) tails represses eukaryotic gene expression by inhibiting efficient translation and committing an mRNA to decay. The CCR4-NOT deadenylase machinery interacts with sequence-specific RNA-binding proteins (RBPs), termed RNA adaptors, to target specific transcripts for deadenylation. In contrast, the PAN2-PAN3 deadenylation complex is thought to be predominantly recruited to mRNAs via interaction with the poly(A) binding protein, raising the question of whether it acts in a transcript-specific manner. Here, using biochemical reconstitution, we show that PAN2-PAN3 can also be recruited to specific RNAs via RNA adaptors, including MEX3, YTHDF and ZFP36 proteins. In cells, we find that a diverse range of RNA adaptors interact with both major deadenylation complexes. Thus, our data suggest that, in addition to CCR4-NOT, PAN2-PAN3 also contributes to the specificity of mRNA degradation and the robustness of post-transcriptional regulation of gene expression.