Visualizing the Higher Order Folding of a Catalytic RNA Molecule
10.1126/science.1989074
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

The higher order folding process of the catalytic RNA derived from the self-splicing intron of Tetrahymena thermophila was monitored with the use of Fe(II)-EDTA-induced free radical chemistry. The overall tertiary structure of the RNA molecule forms cooperatively with the uptake of at least three magnesium ions. Local folding transitions display different metal ion dependencies, suggesting that the RNA tertiary structure assembles through a specific folding intermediate before the catalytic core is formed. Enzymatic activity, assayed with an RNA substrate that is complementary to the catalytic RNA active site, coincides with the cooperative structural transition. The higher order RNA foldings produced by Mg(II), Ca(II), and Sr(II) are similar; however, only the Mg(II)-stabilized RNA is catalytically active. Thus, these results directly demonstrate that divalent metal ions participate in general folding of the ribozyme tertiary structure, and further indicate a more specific involvement of Mg(II) in catalysis.

Bibliography

Celander, D. W., & Cech, T. R. (1991). Visualizing the Higher Order Folding of a Catalytic RNA Molecule. Science, 251(4992), 401–407.

Authors 2
  1. Daniel W. Celander (first)
  2. Thomas R. Cech (additional)
References 69 Referenced 260
  1. ALTMAN, S, RIBONUCLEASE-P - AN ENZYME WITH A CATALYTIC RNA SUBUNIT, ADVANCES IN ENZYMOLOGY AND RELATED AREAS OF MOLECULAR BIOLOGY 62: 1 (1989). / ADVANCES IN ENZYMOLOGY AND RELATED AREAS OF MOLECULAR BIOLOGY (1989)
  2. BEAUDRY, A.A., MINIMUM SECONDARY STRUCTURE REQUIREMENTS FOR CATALYTIC ACTIVITY OF A SELF-SPLICING GROUP-I INTRON, BIOCHEMISTRY 29: 6534 (1990). (10.1021/bi00479a027) / BIOCHEMISTRY (1990)
  3. 10.1016/0092-8674(86)90443-5
  4. Been, M. D., Cold Spring Harbor Symposia on Quantitative Biology 52: 147 (1987). (10.1101/SQB.1987.052.01.019) / Cold Spring Harbor Symposia on Quantitative Biology (1987)
  5. BOGUSKI, M.S., IDENTIFICATION OF A CYTIDINE-SPECIFIC RIBONUCLEASE FROM CHICKEN LIVER, JOURNAL OF BIOLOGICAL CHEMISTRY 255: 2160 (1980). (10.1016/S0021-9258(19)86007-6) / JOURNAL OF BIOLOGICAL CHEMISTRY (1980)
  6. BOYLE, J, SEQUENTIAL FOLDING OF TRANSFER-RNA - A NUCLEAR MAGNETIC-RESONANCE STUDY OF SUCCESSIVELY LONGER TRANSFER-RNA FRAGMENTS WITH A COMMON 5' END, JOURNAL OF MOLECULAR BIOLOGY 139: 601 (1980). (10.1016/0022-2836(80)90051-0) / JOURNAL OF MOLECULAR BIOLOGY (1980)
  7. BURKE, J.M., MOLECULAR-GENETICS OF GROUP-I INTRONS - RNA STRUCTURES AND PROTEIN FACTORS REQUIRED FOR SPLICING - A REVIEW, GENE 73: 273 (1988). (10.1016/0378-1119(88)90493-3) / GENE (1988)
  8. BURKE, J.M., STRUCTURAL CONVENTIONS FOR GROUP-I INTRONS, NUCLEIC ACIDS RESEARCH 15: 7217 (1987). (10.1093/nar/15.18.7217) / NUCLEIC ACIDS RESEARCH (1987)
  9. 10.1146/annurev.bi.59.070190.002551
  10. CECH, T.R., CONSERVED SEQUENCES AND STRUCTURES OF GROUP-I INTRONS - BUILDING AN ACTIVE-SITE FOR RNA CATALYSIS - A REVIEW, GENE 73: 259 (1988). (10.1016/0378-1119(88)90492-1) / GENE (1988)
  11. 10.1126/science.2438771
  12. CELANDER, D.W., IRON(II)-ETHYLENEDIAMINETETRAACETIC ACID-CATALYZED CLEAVAGE OF RNA AND DNA OLIGONUCLEOTIDES - SIMILAR REACTIVITY TOWARD SINGLE-STRANDED AND DOUBLE-STRANDED FORMS, BIOCHEMISTRY 29: 1355 (1990). (10.1021/bi00458a001) / BIOCHEMISTRY (1990)
  13. CELANDER D.W. unpublished data.
  14. CHANDRY S COMMUNICATION.
  15. Creighton T. E. Proteins Structure and Molecular Principles (1983).
  16. Crothers D. M Transfer RNA: Structure Properties and Recognition (1979).
  17. DANCHIN, A, NEW METHOD FOR SPECIFIC LABELING OF TRANSFER-RNA - PRELIMINARY RESULTS ON YEAST TRANSFER-RNA PHE, BIOCHIMIE 54: 333 (1972). (10.1016/S0300-9084(72)80212-8) / BIOCHIMIE (1972)
  18. 10.1038/300719a0
  19. DONISKELLER, H, MAPPING ADENINES, GUANINES, AND PYRIMIDINES IN RNA, NUCLEIC ACIDS RESEARCH 4: 2527 (1977). (10.1093/nar/4.8.2527) / NUCLEIC ACIDS RESEARCH (1977)
  20. DOUDNA, J.A., MINIRIBOZYMES, SMALL DERIVATIVES OF THE SUNY INTRON, ARE CATALYTICALLY ACTIVE, MOLECULAR AND CELLULAR BIOLOGY 9: 5480 (1989). / MOLECULAR AND CELLULAR BIOLOGY (1989)
  21. 10.1038/339519a0
  22. DOWNS, W.D., BIOCHEMISTRY-US 29: 5605 (1990). (10.1021/bi00475a027) / BIOCHEMISTRY-US (1990)
  23. FLOR, P.J., A CONSERVED BASE PAIR WITHIN HELIX-P4 OF THE TETRAHYMENA RIBOZYME HELPS TO FORM THE TERTIARY STRUCTURE REQUIRED FOR SELF-SPLICING, EMBO JOURNAL 8: 3391 (1989). (10.1002/j.1460-2075.1989.tb08503.x) / EMBO JOURNAL (1989)
  24. FRESCO, J.R., TERTIARY STRUCTURE IN TRANSFER RIBONUCLEIC ACIDS, COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY 31: 527 (1966). (10.1101/SQB.1966.031.01.068) / COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY (1966)
  25. GOLDENBERG, D.P., GENETIC-STUDIES OF PROTEIN STABILITY AND MECHANISMS OF FOLDING, ANNUAL REVIEW OF BIOPHYSICS AND BIOPHYSICAL CHEMISTRY 17: 481 (1988). (10.1146/annurev.bb.17.060188.002405) / ANNUAL REVIEW OF BIOPHYSICS AND BIOPHYSICAL CHEMISTRY (1988)
  26. 10.1021/bi00443a017
  27. 10.1016/0092-8674(83)90117-4
  28. 10.1021/bi00438a002
  29. HASELOFF, J, SIMPLE RNA ENZYMES WITH NEW AND HIGHLY SPECIFIC ENDORIBONUCLEASE ACTIVITIES, NATURE 334: 585 (1988). (10.1038/334585a0) / NATURE (1988)
  30. 10.1021/bi00496a003
  31. 10.1021/bi00496a004
  32. HERSCHLAG D COMMUNICATION.
  33. 10.1038/344405a0
  34. HERTZBERG, R.P., CLEAVAGE OF DNA WITH METHIDIUMPROPYL-EDTA-IRON(II) - REACTION CONDITIONS AND PRODUCT ANALYSES, BIOCHEMISTRY 23: 3934 (1984). (10.1021/bi00312a022) / BIOCHEMISTRY (1984)
  35. HEUER T unpublished data.
  36. HOLBROOK, S.R., RNA-LIGAND INTERACTIONS - (I)MAGNESIUM BINDING-SITES IN YEAST TRANSFER-RNAPHE, NUCLEIC ACIDS RESEARCH 4: 2811 (1977). (10.1093/nar/4.8.2811) / NUCLEIC ACIDS RESEARCH (1977)
  37. JACK, A, CRYSTALLOGRAPHIC STUDY OF METAL-BINDING TO YEAST PHENYLALANINE TRANSFER-RNA, JOURNAL OF MOLECULAR BIOLOGY 111: 315 (1977). (10.1016/S0022-2836(77)80054-5) / JOURNAL OF MOLECULAR BIOLOGY (1977)
  38. JAEGER, J.A., MELTING AND CHEMICAL MODIFICATION OF A CYCLIZED SELF-SPLICING GROUP-I INTRON - SIMILARITY OF STRUCTURES IN 1-M NA+, IN 10 MM MG-2+, AND IN THE PRESENCE OF SUBSTRATE, BIOCHEMISTRY 29: 10147 (1990). (10.1021/bi00496a002) / BIOCHEMISTRY (1990)
  39. JAENICKE, R, FOLDING AND ASSOCIATION OF PROTEINS, PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY 49: 117 (1987). (10.1016/0079-6107(87)90011-3) / PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY (1987)
  40. JEZEWSKA, M.J., CORRECTION, BIOCHEMISTRY 29: 5220 (1990). / BIOCHEMISTRY (1990)
  41. JOYCE, G.F., CATALYTIC ACTIVITY IS RETAINED IN THE TETRAHYMENA GROUP-I INTRON DESPITE REMOVAL OF THE LARGE EXTENSION OF ELEMENT P5, NUCLEIC ACIDS RESEARCH 17: 7879 (1989). (10.1093/nar/17.19.7879) / NUCLEIC ACIDS RESEARCH (1989)
  42. KAYNE, M, CATION REQUIREMENTS OF ISOLEUCYL TRANSFER-RNA SYNTHETASE FROM ESCHERICHIA-COLI, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 46: 1285 (1972). (10.1016/S0006-291X(72)80114-1) / BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (1972)
  43. KIM, P.S., SPECIFIC INTERMEDIATES IN THE FOLDING REACTIONS OF SMALL PROTEINS AND THE MECHANISM OF PROTEIN FOLDING, ANNUAL REVIEW OF BIOCHEMISTRY 51: 459 (1982). (10.1146/annurev.bi.51.070182.002331) / ANNUAL REVIEW OF BIOCHEMISTRY (1982)
  44. KIM, P.S., INTERMEDIATES IN THE FOLDING REACTIONS OF SMALL PROTEINS, ANNUAL REVIEW OF BIOCHEMISTRY 59: 631 (1990). (10.1146/annurev.bi.59.070190.003215) / ANNUAL REVIEW OF BIOCHEMISTRY (1990)
  45. 10.1016/0092-8674(82)90414-7
  46. 10.1126/science.2501870
  47. 10.1016/S0300-9084(82)80349-0
  48. 10.1016/0378-1119(89)90026-7
  49. 10.1038/342391a0
  50. MURPHY F.L. COMMUNICATION.
  51. MURPHY, F.L., ALTERATION OF SUBSTRATE-SPECIFICITY FOR THE ENDORIBONUCLEOLYTIC CLEAVAGE OF RNA BY THE TETRAHYMENA RIBOZYME, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 86: 9218 (1989). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1989)
  52. NAZAR R.N. COMMUNICATION.
  53. 10.1016/S0021-9258(19)39629-2
  54. 10.1073/pnas.87.21.8187
  55. QUIGLEY, G.J., STRUCTURAL-ANALYSIS OF SPERMINE AND MAGNESIUM-ION BINDING TO YEAST PHENYLALANINE TRANSFER-RNA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 75: 64 (1978). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1978)
  56. ROBILLARD, G.T., NUCLEAR MAGNETIC-RESONANCE STUDY OF SECONDARY AND TERTIARY STRUCTURE IN YEAST TRANSFER-RNA-PHE, BIOCHEMISTRY 16: 5261 (1977). (10.1021/bi00643a016) / BIOCHEMISTRY (1977)
  57. SYMONS, R.H., SELF-CLEAVAGE OF RNA IN THE REPLICATION OF SMALL PATHOGENS OF PLANTS AND ANIMALS, TRENDS IN BIOCHEMICAL SCIENCES 14: 445 (1989). (10.1016/0968-0004(89)90103-5) / TRENDS IN BIOCHEMICAL SCIENCES (1989)
  58. 10.1038/322083a0
  59. TULLIUS, T.D., HYDROXYL RADICAL FOOTPRINTING - A HIGH-RESOLUTION METHOD FOR MAPPING PROTEIN DNA CONTACTS, METHODS IN ENZYMOLOGY 155: 537 (1987). (10.1016/0076-6879(87)55035-2) / METHODS IN ENZYMOLOGY (1987)
  60. TULLIUS, T.D., HYDROXYL RADICAL FOOTPRINTING - HIGH-RESOLUTION INFORMATION ABOUT DNA PROTEIN CONTACTS AND APPLICATION TO LAMBDA-REPRESSOR AND CRO PROTEIN, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 5469 (1986). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1986)
  61. 10.1126/science.2996145
  62. UHLENBECK, O.C., A SMALL CATALYTIC OLIGORIBONUCLEOTIDE, NATURE 328: 596 (1987). (10.1038/328596a0) / NATURE (1987)
  63. van der Horst, G., Proceedings of the National Academy of Sciences of the United States of America 88: 184 (1991). / Proceedings of the National Academy of Sciences of the United States of America (1991)
  64. 10.1038/321133a0
  65. WILLIAMS, A.P., LASER TEMPERATURE-JUMP, SPECTROSCOPIC, AND THERMODYNAMIC STUDY OF SALT EFFECTS ON DUPLEX FORMATION BY DGCATGC, BIOCHEMISTRY 28: 4283 (1989). (10.1021/bi00436a025) / BIOCHEMISTRY (1989)
  66. WU, H.N., HUMAN HEPATITIS-DELTA VIRUS-RNA SUBFRAGMENTS CONTAIN AN AUTOCLEAVAGE ACTIVITY, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 86: 1831 (1989). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1989)
  67. 10.1021/bi00425a008
  68. 10.1038/324429a0
  69. 10.1126/science.3941911
Dates
Type When
Created 18 years, 10 months ago (Oct. 5, 2006, 6:10 p.m.)
Deposited 1 year, 7 months ago (Jan. 11, 2024, 10:01 p.m.)
Indexed 6 days, 12 hours ago (Aug. 26, 2025, 3:07 a.m.)
Issued 34 years, 7 months ago (Jan. 25, 1991)
Published 34 years, 7 months ago (Jan. 25, 1991)
Published Print 34 years, 7 months ago (Jan. 25, 1991)
Funders 0

None

@article{Celander_1991, title={Visualizing the Higher Order Folding of a Catalytic RNA Molecule}, volume={251}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1989074}, DOI={10.1126/science.1989074}, number={4992}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Celander, Daniel W. and Cech, Thomas R.}, year={1991}, month=jan, pages={401–407} }