Pan2-Pan3 is a conserved complex involved in the shortening of mRNA poly(A)
tails, the initial step in eukaryotic mRNA turnover. We show that recombinant
Saccharomyces cerevisiae Pan2-Pan3 can deadenylate RNAs in vitro without needing
the poly(A)-binding protein Pab1. The crystal structure of an active ~200-kDa
core complex reveals that Pan2 and Pan3 interact with an unusual 1:2
stoichiometry imparted by the asymmetric nature of the Pan3 homodimer. An
extended region of Pan2 wraps around Pan3 and provides a major anchoring point
for complex assembly. A Pan2 module formed by the pseudoubiquitin-hydrolase and
RNase domains latches onto the Pan3 pseudokinase with intertwined interactions
that orient the deadenylase active site toward the A-binding site of the
interacting Pan3. The molecular architecture of Pan2-Pan3 suggests how the
nuclease and its pseudokinase regulator act in synergy to promote deadenylation.
