Structural basis for protein-free catalysis by ribonuclease P ribozyme.

Lee, Yun-Tzai; Degenhardt, Maximilia F S; Skeparnias, Ilias; Chen, Szu-Yun; Bhoge, Bapurao A; Tarasov, Sergey G; Dyba, Marzena A; Zhang, Jinwei et al. · Nat Commun · 2026

basic_science · Level V

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Abstract

Ribonuclease P (RNase P) is an essential metallonuclease found in all three domains of life. However, the structural basis for the ancient RNase P RNA component acting alone as a ribozyme and catalytic metal-ion chemistry remains unknown. We report a series of cryo-EM structures, at resolutions of 2.8-3.5 Å, of the Geobacillus stearothermophilus RNase P aporibozyme (apoE) in various states of the catalytic cycle. The formation of both the tetraloop/tetraloop-receptor interaction and the interdigitated double T-loop motif in the substrate-specificity domain facilitates substrate binding. The apoE uses two metal ions for catalysis, suggesting a catalytic mechanism and evolutionary importance of the RNase P ribozyme to function without its protein component. Together, our data portray the regulatory RNA-RNA interfaces, dynamic structures, and cation traffic that confer function to a trans-acting ribozyme.