mRNA decay is a key determinant of gene regulation, initiated by the shortening of mRNA poly(A) tails by the CCR4-NOT deadenylation complex. Specificity is achieved through RNA adaptors—RNA-binding proteins that recruit CCR4-NOT to specific substrate mRNAs in a regulated manner. However, the molecular mechanisms underlying this specificity remain unclear in many cases. In this study, we applied crosslinking MS to investigate the interaction between the fission yeast RNA-binding protein Puf3 and the Ccr4-Not complex.