TY - JOUR
T1 - Cellular conditions of weakly chelated magnesium ions strongly promote RNA stability and catalysis
AU - Yamagami, Ryota
AU - Bingaman, Jamie L.
AU - Frankel, Erica A.
AU - Bevilacqua, Philip C.
N1 - Funding Information:
We thank Dr. R. Gillilan and Dr. L. Pollack for help with the SAXS experiments and Dr. N.H. Yennawar and K. Leamy for assistance on the SAXS data analysis. This work is conducted at the Cornell High Energy Synchrotron Source (CHESS), which is supported by the National Science Foundation and the National Institutes of Health/National Institute of General Medical Sciences under NSF award DMR-0936384, using the Macromolecular Diffraction at CHESS (MacCHESS) facility, which is supported by GM-103485 from the National Institutes of Health, through its National Institute of General Medical Sciences. We thank K. Messina for assistance with fast hand-mixing reaction time points and members of Bevilacqua group for discussions and suggestions. This study was supported by NIH grant R01-GM110237. We are grateful to the Uehara Memorial Foundation for supporting R.Y.
Funding Information:
We thank Dr. R. Gillilan and Dr. L. Pollack for help with the SAXS experiments and Dr. N.H. Yennawar and K. Leamy for assistance on the SAXS data analysis. This work is conducted at the Cornell High Energy Synchrotron Source (CHESS), which is supported by the National Science Foundation and the National Institutes of Health/National Institute of General Medical Sciences under NSF award DMR-0936384, using the Macromolecular Diffraction at CHESS (MacCHESS) facility, which is supported by GM- 103485 from the National Institutes of Health, through its National Institute of General Medical Sciences. We thank K. Messina for assistance with fast hand-mixing reaction time points and members of Bevilacqua group for discussions and suggestions. This study was supported by NIH grant R01-GM110237. We are grateful to the Uehara Memorial Foundation for supporting R.Y.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Most RNA folding studies have been performed under non-physiological conditions of high concentrations (≥10 mM) of Mg2+ free, while actual cellular concentrations of Mg2+ free are only ∼1 mM in a background of greater than 50 mM Mg2+ total. To uncover cellular behavior of RNA, we devised cytoplasm mimic systems that include biological concentrations of amino acids, which weakly chelate Mg2+. Amino acid-chelated Mg2+ (aaCM) of ∼15 mM dramatically increases RNA folding and prevents RNA degradation. Furthermore, aaCM enhance self-cleavage of several different ribozymes, up to 100,000-fold at Mg2+ free of just 0.5 mM, indirectly through RNA compaction. Other metabolites that weakly chelate magnesium offer similar beneficial effects, which implies chelated magnesium may enhance RNA function in the cell in the same way. Overall, these results indicate that the states of Mg2+ should not be limited to free and bound only, as weakly bound Mg2+ strongly promotes RNA function under cellular conditions.
AB - Most RNA folding studies have been performed under non-physiological conditions of high concentrations (≥10 mM) of Mg2+ free, while actual cellular concentrations of Mg2+ free are only ∼1 mM in a background of greater than 50 mM Mg2+ total. To uncover cellular behavior of RNA, we devised cytoplasm mimic systems that include biological concentrations of amino acids, which weakly chelate Mg2+. Amino acid-chelated Mg2+ (aaCM) of ∼15 mM dramatically increases RNA folding and prevents RNA degradation. Furthermore, aaCM enhance self-cleavage of several different ribozymes, up to 100,000-fold at Mg2+ free of just 0.5 mM, indirectly through RNA compaction. Other metabolites that weakly chelate magnesium offer similar beneficial effects, which implies chelated magnesium may enhance RNA function in the cell in the same way. Overall, these results indicate that the states of Mg2+ should not be limited to free and bound only, as weakly bound Mg2+ strongly promotes RNA function under cellular conditions.
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U2 - 10.1038/s41467-018-04415-1
DO - 10.1038/s41467-018-04415-1
M3 - Article
C2 - 29858572
AN - SCOPUS:85047558001
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2149
ER -