Small RNAs shown to make copies of themselves

A research team identified a 45-base ribozyme, QT-45, that can assemble copies of RNA strands and—rarely and slowly—produce a copy of its own sequence; the enzyme works by joining short RNA fragments and copies with about 95% fidelity.

Researchers report a very short RNA enzyme that can assemble copies of RNA strands, including a copy of its own sequence. The molecule, called QT-45, is 45 bases long and was obtained from pools of randomized short RNAs through rounds of selection and mutation. QT-45 links short RNA fragments and can add clusters of three bases or single bases more slowly, and in at least one experiment it synthesized a strand that paired with and then recreated its own sequence over months. The enzyme functions with mixtures of small RNA fragments, shows about 95 percent copying fidelity, and tolerates little change to its own sequence. Key findings: - The characterized enzyme is QT-45, a 45-base ribozyme derived from an initial 51-base variant called QT-51 after rounds of selection and mutagenesis. - The discovery began with pools of randomized RNAs (40–80 bases) and tag-based selection for ligation activity, followed by further selection and shortening to QT-45. - QT-45 can ligate three-base RNA fragments, work with two-base fragments, and add single bases less efficiently; its active half life exceeded 100 days in tests. - The ribozyme copied templates that included self-complementary regions and produced an active small ribozyme; it also synthesized a sequence that base-pairs with itself and then produced a copy of itself, although this was slow and inefficient. - Average copying fidelity measured about 95 percent, corresponding to roughly two to three errors per self-copying event. - The authors note QT-45 underwent about 18 rounds of selection and that multiple ligases were found in a small sample, implying many such short ligating RNAs may exist. Summary: The study demonstrates that very short ribozymes can catalyze RNA assembly, including rare self-copying events, using pools of short RNA fragments. The researchers report modest activity and fidelity for QT-45 after limited rounds of selection and describe further laboratory selection and broader searches as likely next steps.