Research Highlight
How did life begin? The RNA World hypothesis proposes that, before DNA and proteins, RNA did everything: it stored genetic information and catalysed its own copying. But there has always been a catch. The RNA enzymes (ribozymes) known to copy RNA were large and complex—often more than 150 nucleotides long. Molecules that big are unlikely to have arisen by chance on the early Earth, and are too complex to copy themselves.
A team led by Philipp Holliger at the MRC Laboratory of Molecular Biology in Cambridge has now challenged that assumption. Rather than refining existing ribozymes, they searched vast pools of random RNA sequences—about 6 × 10¹² unique sequences—for any that could copy RNA. After 11 rounds of selection, they identified three small RNA motifs with polymerase activity. Further directed evolution and truncation yielded QT45, a ribozyme just 45 nucleotides long.
Despite its small size, QT45 can copy RNA templates using trinucleotide triphosphate (triplet) building blocks in mildly alkaline eutectic ice. Crucially, it can synthesize both its complementary strand—using a random triplet pool at 94.1% per-nucleotide fidelity—and a copy of itself using defined substrates. Both reactions yielded approximately 0.2% product over 72 days.
The system is not yet self-sustaining. Copying is slow and yields are low, so a continuous cycle of replication remains to be demonstrated. But the finding changes the odds: the discovery of polymerase activity in such a small RNA motif suggests that polymerase ribozymes are more abundant in RNA sequence space than previously thought.
For RNA scientists, QT45 is also a reminder that functional RNA may be hiding in sequence space we have barely explored.
Reference: Gianni E, et al. A small polymerase ribozyme that can synthesize itself and its complementary strand. Science 391, 1022–1028 (2026). doi:10.1126/science.adt2760