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A specific monovalent metal ion integral to the AA platform of the RNA tetraloop receptor

Nature Structural Biology volume 5, pages 986–992 (1998)Cite this article

Abstract

Metal ions are essential for the folding and activity of large catalytic RNAs. While divalent metal ions have been directly implicated in RNA tertiary structure formation, the role of monovalent ions has been largely unexplored. Here we report the first specific monovalent metal ion binding site within a catalytic RNA. As seen crystallographically, a potassium ion is coordinated immediately below AA platforms of the Tetrahymena ribozyme P4-P6 domain, including that within the tetraloop receptor. Interference and kinetic experiments demonstrate that potassium ion binding within the tetraloop receptor stabilizes the folding of the P4-P6 domain and enhances the activity of the Azoarcus group I intron. Since a monovalent ion binding site is integral to the tetraloop receptor, a tertiary structural motif that occurs frequently in RNA, monovalent metal ions are likely to participate in the folding and activity of a wide diversity of RNAs.

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Figure 1: Adenosine platforms within the P4-P6 domain of the Tetrahymena group I intron9.
Figure 2: Thallium binding sites in the P4-P6 domain.
Figure 3: Nucleotide analog interference mapping of the P4-P6 domain with S6GαS.
Figure 4: Interference mapping of the Azoarcus group I intron.

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Acknowledgements

We wish to thank P. B. Moore and J. R. Williamson for critical comments on the manuscript. R.P.R. and J.H.C. were supported by the NIH and A.R.F is a Fellow of the Jane Coffin Childs Memorial Fund for Medical Research. J. S.-S. is a Fellow of the NIH. S.A.S. and J.A.D. are both supported by Beckman Young Investigator Awards and the Searle Foundation. J.A.D. is a Lucille P. Markey Scholar and a David and Lucile Packard Foundation Fellow. This work was funded by an NSF CAREER award and a JFRA from the ACS to S.A.S., and by an NIH grant to J.A.D.

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Author notes

  1. Jamie H.Cate

    Present address: University of California, Santa Cruz, California, 95064, USA

Authors and Affiliations

  1. Department of Molecular Biophysics and Biochemistry, Center for Chemical Biology, Yale University, New Haven, 06520, Connecticut, USA

    Soumitra Basu, Juliane Strauss-Soukup & Scott A. Strobel

  2. Department of Molecular Biophysics and Biochemistry, Center for Structural Biology, Yale University, New Haven, 06520, Connecticut, USA

    Robert P. Rambo, Jamie H.Cate, Adrian R. Ferré-D´Amaré & Jennifer A. Doudna

  3. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, 06520 , Connecticut, USA

    Robert P. Rambo & Jennifer A. Doudna

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Correspondence to Scott A. Strobel or Jennifer A. Doudna.

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Basu, S., P. Rambo, R., Strauss-Soukup, J. et al. A specific monovalent metal ion integral to the AA platform of the RNA tetraloop receptor. Nat Struct Mol Biol 5, 986–992 (1998). https://doi.org/10.1038/2960

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