Figure 8.

Cartoon that summarizes our findings. The RNA (red, dashed red) enters the exosome barrel (gray, sand) through the neck and can interact with one of three active sites (green circles). The substrate jumps between these three active sites with frequencies of ∼1700 s⁻¹ (rounded dashed arrows). The catalytic cleavage rates are in the order of 10 s⁻¹ (scissor symbol), two orders of magnitude slower than the RNA jumping rate. Only 1 in 100 RNA:exosome encounters results in a catalytic reaction. The exosome:RNA nM affinity interactions through the neck region keep the 3′ end of the RNA in the exosome barrel. The high concentration of active sites and substrate in the barrel of the exosome ensures that the 3′ end of the RNA is always in contact with one of the active sites.