Draper, D. E., Grilley, D. & Soto, A. M. Ions and RNA folding. Annu. Rev. Biophys. Biomol. Struct. 34, 221–243 https://doi.org/10.1146/annurev.biophys.34.040204.144511 (2005).
Bowman, J. C., Lenz, T. K., Hud, N. V. & Williams, L. D. Cations in charge: magnesium ions in RNA folding and catalysis. Curr. Opin. Struct. Biol. 22, 262–272 https://doi.org/10.1016/j.sbi.2012.04.006 (2012).
Hayes, R. L. et al. Magnesium fluctuations modulate RNA dynamics in the SAM-I riboswitch. J. Am. Chem. Soc. 134, 12043–12053 https://doi.org/10.1021/ja301454u (2012).
Zheng, H., Shabalin, I. G., Handing, K. B., Bujnicki, J. M. & Minor, W. Magnesium-binding architectures in RNA crystal structures: validation, binding preferences, classification and motif detection. Nucleic Acids Res. 43, 3789–3801 https://doi.org/10.1093/nar/gkv225 (2015).
Al-Hashimi, H. M. & Walter, N. G. RNA dynamics: it is about time. Curr. Opin. Struct. Biol. 18, 321–329 https://doi.org/10.1016/j.sbi.2008.04.004 (2008).
Ganser, L. R., Kelly, M. L., Herschlag, D. & Al-Hashimi, H. M. The roles of structural dynamics in the cellular functions of RNAs. Nat. Rev. Mol. Cell Biol. 20, 474–489 https://doi.org/10.1038/s41580-019-0136-0 (2019).
Bothe, J. R. et al. Characterizing RNA dynamics at atomic resolution using solution-state NMR spectroscopy. Nat. Methods 8, 919–931 https://doi.org/10.1038/nmeth.1735 (2011).
Bottaro, S., Bussi, G., Kennedy, S. D., Turner, D. H. & Lindorff-Larsen, K. Conformational ensembles of RNA oligonucleotides from integrating NMR and molecular simulations. Sci. Adv. 4, eaar8521 https://doi.org/10.1126/sciadv.aar8521 (2018).
Sponer, J. et al. RNA structural dynamics as captured by molecular simulations: a comprehensive overview. Chem. Rev. 118, 4177–4338 https://doi.org/10.1021/acs.chemrev.7b00427 (2018).
Degenhardt, M. F. S. et al. Determining structures of RNA conformers using AFM and deep neural networks. Nature 637, 1234–1243 https://doi.org/10.1038/s41586-024-07559-x (2025).
Lee, Y. T. et al. The conformational space of RNase P RNA in solution. Nature 637, 1244–1251 https://doi.org/10.1038/s41586-024-08336-6 (2025).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290 https://doi.org/10.1038/Nmeth.4169 (2017).
Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 https://doi.org/10.1016/j.jsb.2012.09.006 (2012).
Lyumkis, D., Brilot, A. F., Theobald, D. L. & Grigorieff, N. Likelihood-based classification of cryo-EM images using FREALIGN. J. Struct. Biol. 183, 377–388 https://doi.org/10.1016/j.jsb.2013.07.005 (2013).
Grant, T., Rohou, A. & Grigorieff, N. cisTEM, user-friendly software for single-particle image processing. eLife https://doi.org/10.7554/eLife.35383 (2018).
Zhong, E. D., Bepler, T., Berger, B. & Davis, J. H. CryoDRGN: reconstruction of heterogeneous cryo-EM structures using neural networks. Nat. Methods 18, 176–185 https://doi.org/10.1038/s41592-020-01049-4 (2021).
Punjani, A. & Fleet, D. J. 3D variability analysis: Resolving continuous flexibility and discrete heterogeneity from single particle cryo-EM. J. Struct. Biol. 213, 107702 https://doi.org/10.1016/j.jsb.2021.107702 (2021).
Degenhardt, H. F. EMCrafter: large-scale cryo-EM simulation toolkit driven by experimental data profiles [computer software]. Zenodo https://doi.org/10.5281/zenodo.16366716 (2025).
Zhang, J. & Ferre, D. A. R. Trying on tRNA for size: RNase P and the T-box riboswitch as molecular rulers. Biomolecules https://doi.org/10.3390/biom6020018 (2016).
Guerrier-Takada, C., Gardiner, K., Marsh, T., Pace, N. & Altman, S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35, 849–857 https://doi.org/10.1016/0092-8674(83)90117-4 (1983).
Niranjanakumari, S., Stams, T., Crary, S. M., Christianson, D. W. & Fierke, C. A. Protein component of the ribozyme ribonuclease P alters substrate recognition by directly contacting precursor tRNA. Proc. Natl Acad. Sci. U.S.A. 95, 15212–15217 https://doi.org/10.1073/pnas.95.26.15212 (1998).
Klemm, B. P. et al. The diversity of ribonuclease P: protein and RNA catalysts with analogous biological functions. Biomolecules https://doi.org/10.3390/biom6020027 (2016).
Riziotis, I. G., Ribeiro, A. J. M., Borkakoti, N. & Thornton, J. M. Conformational variation in enzyme catalysis: a structural study on catalytic residues. J. Mol. Biol. 434, 167517 https://doi.org/10.1016/j.jmb.2022.167517 (2022).
Sengupta, R. N. et al. An active site rearrangement within the Tetrahymena group I ribozyme releases nonproductive interactions and allows formation of catalytic interactions. RNA 22, 32–48 https://doi.org/10.1261/rna.053710.115 (2016).
Giarimoglou, N., Kouvela, A., Zhang, J., Stamatopoulou, V. & Stathopoulos, C. Structural idiosyncrasies of glycyl T-box riboswitches among pathogenic bacteria. RNA 30, 1328–1344 https://doi.org/10.1261/rna.080071.124 (2024).
Wu, J. et al. Cryo-EM structure of the human ribonuclease P holoenzyme. Cell 175, 1393–1404.e1311 https://doi.org/10.1016/j.cell.2018.10.003 (2018).
Wan, F. et al. Cryo-electron microscopy structure of an archaeal ribonuclease P holoenzyme. Nat. Commun. 10, 2617 https://doi.org/10.1038/s41467-019-10496-3 (2019).
Torres-Larios, A., Swinger, K. K., Krasilnikov, A. S., Pan, T. & Mondragon, A. Crystal structure of the RNA component of bacterial ribonuclease P. Nature 437, 584–587 https://doi.org/10.1038/nature04074 (2005).
Wang, J., Liu, Z., Frank, J. & Moore, P. B. Identification of ions in experimental electrostatic potential maps. IUCrJ 5, 375–381 https://doi.org/10.1107/S2052252518006292 (2018).
Leonarski, F., D’Ascenzo, L. & Auffinger, P. Mg2+ ions: do they bind to nucleobase nitrogens?. Nucleic Acids Res. 45, 987–1004 https://doi.org/10.1093/nar/gkw1175 (2017).
Kretsch, R. C. et al. Complex water networks visualized by cryogenic electron microscopy of RNA. Nature 642, 250–259 https://doi.org/10.1038/s41586-025-08855-w (2025).
Leonarski, F., Henning-Knechtel, A., Kirmizialtin, S., Ennifar, E. & Auffinger, P. Principles of ion binding to RNA inferred from the analysis of a 1.55 Å resolution bacterial ribosome structure – part I: Mg2+. Nucleic Acids Res. https://doi.org/10.1093/nar/gkae1148 (2025).
Alonso, D. & Mondragon, A. Mechanisms of catalytic RNA molecules. Biochem. Soc. Trans. 49, 1529–1535 https://doi.org/10.1042/BST20200465 (2021).
Walter, N. G. Ribozyme catalysis revisited: is water involved?. Mol. Cell 28, 923–929 https://doi.org/10.1016/j.molcel.2007.12.001 (2007).
Masquida, B. & Westhof, E. RNase P: at last, the key finds its lock. RNA 17, 1615–1618 https://doi.org/10.1261/rna.2841511 (2011).
Auffinger, P., Louisemay, S. & Westhof, E. Multiple molecular-dynamics simulations of the anticodon loop of tRNAAsp in aqueous-solution with counterions. J. Am. Chem. Soc. 117, 6720–6726 https://doi.org/10.1021/ja00130a011 (1995).
Misra, V. K. & Draper, D. E. The linkage between magnesium binding and RNA folding. J. Mol. Biol. 317, 507–521 https://doi.org/10.1006/jmbi.2002.5422 (2002).
Guth-Metzler, R. et al. Goldilocks and RNA: where Mg2+ concentration is just right. Nucleic Acids Res. 51, 3529–3539 https://doi.org/10.1093/nar/gkad124 (2023).
Kumawat, A. & Chakrabarty, S. Hidden electrostatic basis of dynamic allostery in a PDZ domain. Proc. Natl Acad. Sci. U.S.A. 114, E5825–E5834 https://doi.org/10.1073/pnas.1705311114 (2017).
Nussinov, R., Ma, B. & Tsai, C. J. Multiple conformational selection and induced fit events take place in allosteric propagation. Biophys. Chem. 186, 22–30 https://doi.org/10.1016/j.bpc.2013.10.002 (2014).
Kar, G., Keskin, O., Gursoy, A. & Nussinov, R. Allostery and population shift in drug discovery. Curr. Opin. Pharmacol. 10, 715–722 https://doi.org/10.1016/j.coph.2010.09.002 (2010).
Chakraborty, A. et al. RNA’s dynamic conformational selection and entropic allosteric mechanism in controlling cascade protein binding events. J. Phys. Chem. Lett. 15, 6115–6125 https://doi.org/10.1021/acs.jpclett.4c00740 (2024).
Misra, V. K. & Draper, D. E. On the role of magnesium ions in RNA stability. Biopolymers 48, 113–135 (1998).
Cate, J. H. et al. Crystal structure of a group I ribozyme domain: principles of RNA packing. Science 273, 1678–1685 https://doi.org/10.1126/science.273.5282.1678 (1996).
Manning, G. S. The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Q. Rev. Biophys. 11, 179–246 https://doi.org/10.1017/s0033583500002031 (1978).
Cunha, R. A. & Bussi, G. Unraveling Mg2+-RNA binding with atomistic molecular dynamics. RNA 23, 628–638 https://doi.org/10.1261/rna.060079.116 (2017).
Degenhardt, H. F. CMM Web Submitter: scripted web interface for parallel file submission and result retrieval from CheckMyMetal (CMM) [computer software]. Zenodo https://doi.org/10.5281/zenodo.16367407 (2025).
Degenhardt, M. F. d. S. RNAIonScan: ion binding mode classifier for RNA [computer software]. Zenodo https://doi.org/10.5281/zenodo.17832303 (2025).