Abstract
The ability of certain RNAs, denoted as ribozymes, to not only store genetic information but also catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth. This, however, might have evolved under extreme environmental conditions, including the deep sea with pressures in the kbar regime. Here we study pressure-induced effects on the self-cleavage of hairpin ribozyme by following structural changes in real-time. Our results suggest that compression of the ribozyme leads to an accelerated transesterification reaction, being the self-cleavage step, although the overall process is retarded in the high-pressure regime. The results reveal that favourable interactions between the reaction site and neighbouring nucleobases are strengthened under pressure, resulting therefore in an accelerated self-cleavage step upon compression. These results suggest that properly engineered ribozymes may also act as piezophilic biocatalysts in addition to their hitherto known properties.
Highlights
The ability of certain RNAs, denoted as ribozymes, to store genetic information and catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth
We explored the self-cleavage step by simulating the activated precursor (AP) state[33] being the hairpin ribozyme (HpRz) structure closest to the transition state, using largescale replica-exchange molecular dynamics simulations at high hydrostatic pressure (HHP) conditions
Our PAGE measurements on wild-type hairpin ribozyme (wt-HpRz) as shown in Fig. 3a confirm that the overall process gets decelerated upon increasing pressure
Summary
The ability of certain RNAs, denoted as ribozymes, to store genetic information and catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth. This self-cleavage reaction involves the nucleophilic attack of the 20-OH group on the adjacent phosphorus atom, resulting in a 20,30-cyclic phosphate and a 50-hydroxyl terminus[4] Discovery of such catalytically active RNAs, which simultaneously can store genetic information and act as biocatalysts, greatly supported the so-called ‘RNA world’ hypothesis, suggesting that extant life arose from molecular precursors where RNA could selfreplicate and ensure proper metabolism. In the realm of HHP conditions, computer simulations have revealed most recently that high pressures stabilize the A-form of RNA folds[40] In addition to such non-reactive simulations, there has been impressive progress on QM/MM studies focusing on the very chemical reaction of ribozymes at ambient conditions, see for instance refs 41–43
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