Researchers evolve 45-nucleotide RNA polymerase

Edoardo Gianni and colleagues at the MRC Laboratory of Molecular Biology reported on Feb. 13, 2026, that they had evolved a 45-nucleotide RNA polymerase ribozyme from short random RNA sequences. The molecule, called QT45, was described in Science as a catalytic RNA that can carry out RNA-templated RNA synthesis using activated trinucleotide building blocks. The paper said QT45 could copy a range of RNA templates despite being far smaller than previously reported polymerase ribozymes. The work adds a new experimental result to long-running efforts to test whether RNA alone could support heredity and replication in early chemical systems. ### Why does 45 nucleotides matter here? Science said previously evolved RNA polymerase ribozymes were generally more than 150 nucleotides long and structurally complex. The paper said that size creates two problems at once: larger ribozymes are harder to copy accurately, and their spontaneous appearance from random sequence pools is less likely than that of shorter RNAs. QT45 was presented as a way around that constraint because its catalytic core is much smaller. (science.org) The MRC Laboratory of Molecular Biology said researchers in Philipp Holliger’s group had spent years working in a field dominated by one ribozyme lineage. Edoardo Gianni said in the institute’s account that many researchers had assumed a polymerase ribozyme “had to be a long RNA sequence” to perform the reaction. The new study reported three small, unrelated RNA sequences with polymerase activity before further evolution and engineering produced QT45. (science.org) ### How did the team find QT45? The researchers used in vitro selection on pools of short, random RNA sequences, according to Science and the MRC Laboratory of Molecular Biology. The idea was to search broadly for any small RNA motifs that could catalyze templated polymerization rather than continue optimizing the larger ribozymes already known in the field. After repeated rounds of selection, the team isolated three active candidates and then improved them through directed evolution and engineering. (mrclmb.ac.uk) UK Research and Innovation said the breakthrough came from generating vast pools of random RNA sequences and selecting those with RNA-copying activity. The institute and UKRI both said QT45 emerged after repeated enrichment for active molecules. ### What can QT45 actually do in the lab? Science said QT45 showed “general RNA polymerase activity” with activated RNA trinucleotide building blocks. (science.org) The paper summary said it copied a variety of RNA templates, including tightly folded sequences and templates encoding a hammerhead endonuclease ribozyme. The central experimental claim was that the ribozyme could synthesize both itself and its complementary strand under laboratory conditions, a combination the authors framed as the two key reactions needed for self-replication. (mrclmb.ac.uk) The MRC Laboratory of Molecular Biology described RNA self-replication as the ability of an RNA molecule to copy both itself and the information encoded in its complementary strand. The institute said previous polymerase ribozymes could copy other RNA molecules but had been too large and complex to copy themselves completely. QT45’s smaller size, the institute said, allowed it to copy all of itself and its template rather than only fragments. (science.org) ### What does the paper say about origins-of-life research? The Science summary said the emergence of a chemical system capable of self-replication and evolution is a critical event in origin-of-life research. The paper placed QT45 within the “RNA world” framework, which proposes that RNA once served as both genetic material and catalyst before the rise of modern protein-and-DNA biology. The authors argued that finding polymerase activity in a much smaller RNA motif reduces the gap between what can be evolved in the lab and what might plausibly emerge from random chemistry. (mrclmb.ac.uk) Edoardo Gianni said in the UKRI release that the result offered “a glimpse” of what early steps of life might have looked like. That interpretation was presented by the institute and UKRI as a consequence of the ribozyme’s small size and its ability to copy both itself and its template. ### What comes next for Gianni and Holliger’s group? (science.org) UK Research and Innovation said the team had already demonstrated the two component reactions needed for self-replication and was now trying to combine them into a self-replication cycle. The next step, as described by the institute, is to link synthesis of QT45 and synthesis of its complementary strand in one experimental system. Science listed Edoardo Gianni and Philipp Holliger as corresponding authors on the Feb. 13, 2026 paper, titled “A small polymerase ribozyme that can synthesize itself and its complementary strand.” (science.org) (mrclmb.ac.uk)