Tiny, 45 base long RNA can make copies of itself

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But the key discovery was that it could synthesize a sequence that base-pairs with itself, and then synthesize itself by copying that sequence. This was extremely ineffective and took several months, but it happened.

Throughout all of these experiments, fidelity averaged about 95 percent, meaning that, in copying itself, it would make an average of two to three errors. While this means that a fair number of copies of it will not be functional, it also means that the raw material for evolutionary selection for better function – random mutations – will be present.

what does it mean

It is reasonable to consider the use of three-base RNA fragments by this enzyme. On the surface, this might seem like a bit of cheating, since current RNA polymerases add one base sequence at a time. But in reality, any chemical environment that can automatically assemble a 45 base long RNA molecule will produce many fragments smaller than that. So in many ways, it may be a more realistic model of the conditions in which life arose.

The authors say that these small fragments may be essential for the activity of QT-45. Small ribozymes probably do not have the ability to copy the base-paired strands of RNA by separating them enzymatically. But in a mixture of lots of small fragments, there is likely to be an equilibrium, with some base-pairing sequences automatically opening up and temporarily base pairing with a small fragment. Working with these base-paired fragments is probably essential for the overall activity of the ribozyme.

Currently, QT-45 is not a dominant enzyme. But researchers say that it has gone through only 18 rounds of selection, which is not much. The most efficient ribozyme polymerase we currently have has been worked on for years by many laboratories. I hope the QT-45 will be given the same attention and will improve significantly over time.

It’s also notable that the team came up with three different ligases in testing a small subset of the potential total RNA population of this size. If that frequency holds, then on the order of 1011 Ligating the ribozyme between sequences of this size. Which increases the possibility that if we search in detail we may find much more. This suggests that the first self-replicating RNA may not be as impossible as it seems at first glance.

Science, 2026. DOI: 10.1126/science.adt2760 (About DOI).



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