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Structure of an RNA polymerase ribozyme replication complex

Strutzenberg, T. S.; Horning, D. P.; Cochrane, W. G.; Andrade, L.; Han, X.; Joyce, G. F.; Lyumkis, D.

2026-08-31 biophysics
10.64898/2026.08.30.748161 bioRxiv
Show abstract

Life began with the emergence of a molecule that could replicate its own genetic material, a task plausibly mediated by an RNA-dependent RNA polymerase ribozyme. Here, we present the structure of such a polymerase ribozyme, bound to RNA substrates comprising the template, primer, and nucleoside triphosphate (NTP) analog. The structure reveals how directed evolution shaped flanking elements around a highly conserved catalytic core derived from the ancestral class I ligase ribozyme. Each element serves as a functional module, positioning the primer-template duplex and incoming NTP within the active site of the enzyme. This emergent domain organization is remarkably similar to the "right hand" configuration of polymerase proteins, suggesting a common functional form for copying nucleic acids, regardless of biopolymer catalyst.

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