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Abstract:
mRNA degradation is an essential component of the gene expression process. Cytoplasmic mRNA decay is typically initiated by the removal of poly(A) tails, a process termed deadenylation, which causes translational repression and, in most cases, triggers irreversible mRNA degradation. The PAN2- PAN3 deadenylase complex functions in both bulk and microRNA-mediated mRNA decay and is directly recruited to microRNA targets by GW182/ TNRC6 proteins. Taking a structural and functional approach, we have identified unusual features that mediate the interaction of PAN3 with PAN2 and TNRC6 proteins, as well as critical residues required for mRNA degradation in vivo. Collectively, our data describes the structural basis for the recruitment of the PAN2-PAN3 complex to microRNA targets by the TNRC6 proteins, and the essential role of PAN3 in coordinating deadenylation with downstream steps of the mRNA decay pathway.
