RNA Folding Pathways

Donald M. Crothers1

1 Yale University, New Haven, Connecticut
Publication Name:  Current Protocols in Nucleic Acid Chemistry
Unit Number:  Unit 11.1
DOI:  10.1002/0471142700.nc1101s02
Online Posting Date:  May, 2001
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


A general overview of the questions and problems in RNA folding is presented. Topics include the differences in the folding problems/questions that apply to RNA versus proteins, methods for determination of final structures, folding versus unfolding, resolution of space and time, and conformational switching.

PDF or HTML at Wiley Online Library

Table of Contents

  • Overview of the Questions
  • How RNA and Proteins Differ in the Folding Problem
  • How We Know the Final Structure
  • Folding Versus Unfolding
  • Resolution in Space and Time
  • Conformational Switching
  • Literature Cited
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
   Bevilacqua, P.C., Kierzek, R., Johnson, K.A., and Turner, D.H. 1992. Dynamics of ribozyme binding of substrate revealed by fluorescence‐detected stopped‐flow methods. Science 258:1355‐1358.
   Breslauer, K.J., Frank, R., Blocker, H., and Marky, L.A. 1986. Predicting DNA duplex stability from the base sequence. Proc. Natl. Acad. Sci. U.S.A. 83:3746‐3750.
   Brion, P., Westhof, E. 1997. Hierarchy and dynamics of RNA folding. Annu. Rev. Biophys. Biomol. Struct. . 26:113‐137.
   Cate, J.H., Gooding, A.R., Podell, E., Zhou, K., Golden, B.L., Kundrot, C.E., Cech, T.R., and Doudna, J.A. 1996. Crystal structure of a group I ribozyme domain: Principles of RNA packing. Science 273:1678‐1685.
   Chen, J.L., Blasco, M.A., and Greider, C.W. 2000. Secondary structure of vertebrate telomerase RNA. Cell 100:503‐514.
   Cole, P.E. and Crothers, D.M. 1972. Conformational changes of transfer ribonucleic acid. Relaxation kinetics of the early melting transition of methionine transfer ribonucleic acid (Escherichia coli). Biochemistry 11:4368‐4374.
   Cole, P.E., Yang, S.K., and Crothers, D.M. 1972. Conformational changes of transfer ribonucleic acid. Equilibrium phase diagrams. Biochemistry 11:4358‐4368.
   Crothers, D.M., Cole, P.E., Hilbers, C.W., and Shulman, R.G. 1974. The molecular mechanism of thermal unfolding of transfer RNA. J. Mol. Biol. 87:63‐88.
   Doherty, E.A. and Doudna, J.A. 1997. The P4‐P6 domain directs higher order folding of the Tetrahymena. ribozyme core. Biochemistry . 36:3159‐3169.
   Draper, D.E. and Gluick, T.C. 1995. Melting studies of RNA unfolding and RNA‐ligand interactions. Methods Enzymol. 259:281‐305.
   Emerick, V.L. and Woodson, S.A. 1994. Fingerprinting the folding of a group I precursor RNA. Proc. Natl. Acad. Sci. U.S.A. 91:9675‐9679.
   Farris, A.D., Koelsch, G., Pruijn, G.J., van Venrooij, W.J., and Harley, J.B. 1999. Conserved features of Y RNAs revealed by automated phylogenetic secondary structure analysis. Nucl. Acids Res. 27:1070‐1078.
   Gluick, T.C., Gerstner, R.B., and Draper, D.E. 1997. Effects of Mg2+, K+, and H+ on an equilibrium between alternative conformations of an RNA pseudoknot. J. Mol. Biol. 270:451‐463.
   Harris, M.E. and Pace, N.R. 1995‐1996. Analysis of the tertiary structure of bacterial RNase P RNA. Mol. Biol. Rep. I22:115‐123.
   Hilbers, C.W., Robilard, G.T., Shulman, R.G., Blake, R.D., Webb, P.K., Fresco, R., and Riesner, D. 1976. Thermal unfolding of yeast glycine transfer RNA. Biochemistry 15:1874‐1882.
   Kruger, K., Grabowski, P.J., Zaug, A.J., Sands, J., Gottschling, D.E., and Cech, T.R. 1982. Self‐splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 32:147‐157.
   LeCuyer, K.A. and Crothers, D.M. 1994. Kinetics of an RNA conformational switch. Proc. Natl. Acad. Sci. U.S.A. 91:3373‐3377.
   Maglott, E.J. and Glick, G.D. 1997. A new method to monitor the rate of conformational transitions in RNA. Nucl. Acids Res. 25:3297‐3301.
   Matthews, D.H., Sabina, J., Zucker, M., and Turner, D.H. 1999. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J. Mol. Biol. 288:911‐940.
   Noller, H.F., Kop, J., Wheaton, V., Brosius, J., Gutell, R.R., Kopylov, A.M., Dohme, F., Herr, W., Stahl, D.A., Gupta, R., and Waese, C.R. 1981. Secondary structure model for 23S ribosomal RNA. Nucl. Acids Res. 9:6167‐6189.
   Pan, J. and Woodson, S.A. 1999. The effect of long‐range loop‐loop interactions on folding of the Tetrahymena self‐splicing RNA. J. Mol. Biol. 294:955‐965.
   Riesner, D., Romer, R., and Maass, G. 1969. Thermodynamic properties of the three conformational transitions of alanine specific transfer RNA from yeast. Biochem. Biophys. Res. Commun. 35:369‐376.
   Riesner, D., Romer, R., and Maass, G. 1970. Kinetic study of the three conformational transitions of alanine specific transfer RNA from yeast. Eur. J. Biochem. 15:85‐91.
   Riesner, D., Maass, G., Thiebe, R., Philippsen, P., and Zachau, H.G. 1973. The conformational transitions in yeast tRNAPhe as studied with tRNAPhe fragments. Eur. J. Biochem. 36:76‐88.
   Sclavi, B., Sullivan, M., Chance, M.R., Brenowitz, M., and Woodson, S.A. 1998. RNA folding at millisecond intervals by synchrotron hydroxyl radical footprinting. Science 279:1940‐1943.
   Tinoco, I. Jr. and Bustamante, C. 1999. How RNA folds. J. Mol. Biol. 293:271‐281.
   Treiber, D.K., Rook, M.S., Zarrinkar, P.P., and Williamson, J.R. 1998. Kinetic intermediates trapped by native interactions in RNA folding. Science 279:1943‐1946.
   Weeks, K.M. and Cech, T.R. 1995. Protein facilitation of group I intron splicing by assembly of the catalytic core and the 5′ splice site domain. Cell 82:221‐230.
   Wu, M. and Tinoco, I. Jr. 1998. RNA folding causes secondary structure rearrangement. Proc. Natl. Acad. Sci. U.S.A. 95:11555‐11560.
   Xia, T., SantaLucia, J. Jr., Burkard, M.E., Kierzek, R., Schroeder, S.J., Jiao, X., Cox, C., and Turner, D.H. 1998. Thermodynamic parameters for an expanded nearest‐neighbor model for formation of RNA duplexes with Watson‐Crick base pairs. Biochemistry 37:14719‐14735.
   Zarrinkar, P.P. and Williamson, J.R. 1994. Kinetic intermediates in RNA folding. Science 265:918‐924.
PDF or HTML at Wiley Online Library