45‑nucleotide ribozyme shown to synthesize copies of itself in laboratory selection

Researchers have isolated an unusually compact catalytic RNA that, under laboratory selection, can assemble complementary sequences and ultimately reproduce its own information. The work addresses a central hurdle for models of life’s emergence: the production of RNA sequences that both store information and reproduce it without proteins. Rather than searching among long, complex molecules, the team screened libraries of short random RNAs — tens of bases long — and enriched for ligation activity using tagged three‑nucleotide fragments in cold, salty reaction conditions. After iterative selection and mutational refinement the population yielded a functional polymerizing ribozyme that was trimmed to 45 nucleotides without losing its core activity. Characterization showed the tiny enzyme most efficiently joins short oligomers of three bases but can also add one or two bases at a time; its operation is slow but the active form endures for well over one hundred days. Copying trials produced complementary strands that could base‑pair with templates and, in at least one instance, led to the reconstruction of the enzyme’s own sequence — a process that required months and occurred with roughly 95 percent per‑base fidelity, corresponding to two to three errors in a full copy. The ribozyme’s function depends heavily on nearly all positions in its sequence, with a central region particularly intolerant to substitution, although a few mutations improved performance, indicating potential for further evolution. The team also estimated the crude abundance of similar ligating sequences within the explored sequence space, implying such activities might arise more frequently than once assumed. Mechanistically, the enzyme appears to exploit pools of short oligomers and transiently open base pairs rather than actively unwinding long duplexes, which fits a prebiotic scenario where short fragments were abundant. The discovery reframes the tradeoff between molecular size and catalytic reach: simplicity can come at the cost of speed and stringency, but stability and the ability to use short building blocks compensate. Practically, this short ribozyme offers a new experimental scaffold that laboratories can quickly iterate on; with additional rounds of selection and engineering its polymerase‑like performance could improve substantially. Conceptually, the result lowers one barrier for RNA‑first hypotheses by demonstrating a plausible, minimal pathway to self‑copying informational polymers. The findings do not yet produce a robust, rapid self‑replicator, but they supply a tractable starting point for both origin‑of‑life research and synthetic biology efforts to recreate minimal replicating systems.