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A polymerase ribozyme that can synthesize both itself and its complementary strand

Gianni, E.; Kwok, S. L. Y.; Wan, C. J. K.; Goeij, K.; Clifton, B.; Attwater, J.; Holliger, P.

2024-10-12 biochemistry
10.1101/2024.10.11.617851 bioRxiv
Show abstract

The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes could constitute such a system, but their large size and structural complexity hinder their self-replication and make their spontaneous emergence improbable. Here we describe QT45: a 45-nucleotide ribozyme, discovered from a random sequence pool, that catalyzes general RNA-templated RNA synthesis using trinucleotide triphosphate substrates. QT45 can synthesize both its complementary strand from a mix of all 64 trinucleotides and a copy of itself using 13 defined trinucleotides and one hexamer as substrates. The discovery of this complex activity in a small ribozyme suggests that polymerase ribozymes may be more abundant in RNA sequence space than anticipated, thereby facilitating the emergence of self-replication.

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