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A natural ribozyme with 3′,5′ RNA ligase activity

Abstract

Using electrophoresis, sequencing and enzymatic digestion, we show that the group I intron from the cyanobacterium Anabaena sp. PCC 7120 catalyzes phosphodiester bond formation using a triphosphate on the 5′-terminal nucleotide, much like protein polymerases and engineered ribozymes. In the process, this ribozyme forms a unique circular RNA that incorporates the exogenous guanosine cofactor added during self-splicing. This finding may have relevance to a prebiotic RNA world and to modern biology.

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Figure 1: Reaction pathways catalyzed by group I introns.
Figure 2: New circular RNA.

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Acknowledgements

We thank A. Zaug for experimental suggestions and insightful discussions; A. Gooding (Howard Hughes Medical Institute) for preparing the T7 RNA polymerase; D. Zappulla (Johns Hopkins University) for the gift of RNase A; the remaining members of the Cech laboratory, as well as H. Nielsen, O. Uhlenbeck, S. Silverman and M. Caruthers, for helpful discussions; and H. Nielsen, S. Silverman, A. Gooding and A. Zaug for careful reading of the manuscript.

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Q.V. and T.R.C. designed the study and wrote the manuscript; Q.V. performed the experiments.

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Correspondence to Quentin Vicens.

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Supplementary Figures 1–9 and Supplementary Methods (PDF 4090 kb)

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Vicens, Q., Cech, T. A natural ribozyme with 3′,5′ RNA ligase activity. Nat Chem Biol 5, 97–99 (2009). https://doi.org/10.1038/nchembio.136

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