A ribozyme that uses lanthanides as cofactor

To explore how an early, RNA-based life form could have functioned, in vitro selection experiments have been used to develop catalytic RNAs (ribozymes) with relevant functions. We previously identified ribozymes that use the prebiotically plausible energy source cyclic trimetaphosphate (cTmp) to convert their 5 '-hydroxyl group to a 5 '-triphosphate. While these ribozymes were developed in the presence of Mg2+, we tested here whether lanthanides could also serve as catalytic cofactors because lanthanides are ideal catalytic cations for this reaction. After an in vitro selection in the presence of Yb3+, several active sequences were isolated, and the most active RNA was analyzed in more detail. This ribozyme required lanthanides for activity, with highest activity at a 10:1 molar ratio of cTmp : Yb3+. Only the four heaviest lanthanides gave detectable signals, indicating a high sensitivity of ribozyme catalysis to the lanthanide ion radius. Potassium and Magnesium did not facilitate catalysis alone but they increased the lanthanide-mediated k(OBS) by at least 100-fold, with both K+ and Mg2+ modulating the ribozyme's secondary structure. Together, these findings show that RNA is able to use the unique properties of lanthanides as catalytic cofactor. The results are discussed in the context of early life forms.

Automated summary

In vitro selection experiments have developed catalytic RNA using cyclic trimetaphosphate as an energy source. Lanthanides can serve as catalytic cofactors for these ribozymes, with a sensitivity to ion radius. Potassium and magnesium enhance the lanthanide-mediated catalysis.