Sisyphus observed: Unraveling the high ATP usage of an RNA chaperone.

DEAD-box proteins are nonprocessive RNA helicases that can function as RNA chaperones by coupling ATP binding and hydrolysis to structural reorganization of RNA. Here, Jarmoskaite et al. quantify the ATP utilization of an RNA chaperone during refolding of a misfolded ribozyme substrate. Strikingly, 100 ATP hydrolysis events are needed per successfully refolded ribozyme, suggesting that each round of unfolding requires ten ATP molecules, since 90% of substrate unfolding cycles only lead back to the kinetically favored misfolded state. This near-Sisyphean effort reveals a potentially conserved model for RNA reorganization by RNA chaperones.