Exposing the kinetic traps in RNA folding

Current Opinion in Structural Biology

Volumn 9, Issue 3, 1999, Pages 339-345

  Treiber, Daniel K ^a   Williamson, James R ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RIBONUCLEASE P; RIBOZYME; RNA;

KINETICS; MUTANT; PRIORITY JOURNAL; REVIEW; RNA CONFORMATION;

EID: 0033150859     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(99)80045-1     Document Type: Article

References (47)

1. Uhlenbeck OC: Keeping RNA happy. RNA 1995, 1:4-6.
2. Weeks KM: Protein-facilitated RNA folding. Curr Opin Struct Biol 1997, 7:336-342. A lucid description of the RNA folding problem and the various roles that proteins can play in the process, including tertiary structure capture, tertiary structure nucleation and RNA folding chaperone activity.
3. Pan J, Thirumalai D, Woodson SA: Folding of RNA involves parallel pathways. J Mol Biol 1997, 273:7-13. The folding of the Tetrahymena group I intron pre-RNA is slowed by kinetic traps that are disrupted by denaturants. A small fraction of the molecules, however, folds rapidly in the absence of denaturants, suggesting the existence of parallel folding pathways. The authors were the first to describe RNA folding in terms of energy landscapes and kinetic partitioning. This description is supported by subsequent findings [5•,29••].
4. 2+-dependent folding of the RNase P ribozyme by a factor of 30, indicating the presence of a kinetic trap.
5. 2+-dependent folding of the Tetrahymena ribozyme. Both traps are diminished by denaturants, whereas a mutation that destabilizes native structure acts selectively at one step. In addition, folding is often characterized by multi-exponential kinetics. These findings are consistent with the suggestion that the folding landscape is rugged [3••].
6. Cole PE, Crothers DM: Conformational changes of transfer ribonucleic acid. Relaxation kinetics of the early melting transition of methionine transfer ribonucleic acid (escherichia coli). Biochemistry 1972, 11:4368-4374.
7. Celander DW, Cech TR: Visualizing the higher order folding of a catalytic RNA molecule. Science 1991, 251:401-407.
8. Zarrinkar PP, Williamson JR: The kinetic folding pathway of the tetrahymena ribozyme reveals possible similarities between RNA and protein folding. Nat Struct Biol 1996, 3:432-438.
9. Hegg LA, Fedor MJ: Kinetics and thermodynamics of intermolecular catalysis by hairpin ribozymes. Biochemistry 1995, 34:15813-15828.
10. 2+ ions that brings the two domains into proximity for docking and catalysis.
11. 2+-dependent event that proceeds with a surprisingly large activation energy. Small RNA motifs are thus not immune to the slow folding process observed for large ribozymes.
12. -1) folding rate. Exon sequences can promote mispairing in the core by inhibiting formation of the substrate helix. This suggests an important role for sequence context in the folding process.
13. Walter NG, Burke JM, Millar DP: Stability of the hairpin ribozyme tertiary structure is governed by the interdomain junction. Nat Struct Biol 1999, 6:in press. Time-resolved fluorescence resonance energy transfer (tr-FRET) studies demonstrate that domain docking in the hairpin ribozyme is most efficient in the context of a four-way junction. tr-FRET, unlike steady-state FRET, can measure the equilibrium distribution of docked and undocked conformers.
14. Brodsky AS, Williamson JR: Solution structure of the HIV-2 TAR-argininamide complex. J Mol Biol 1997, 267:624-639. The argininamide-binding site in HIV-2 TAR is set up by a bulge structure that opens the major groove for recognition. A base triple is required to form the binding pocket and the bulge is unstructured in the absence of bound ligand.
15. Zimmermann GR, Jenison RD, Wick CL, Simorre JP, Pardi A: Interlocking structural motifs mediate molecular discrimination by a theophylline-binding RNA. Nat Struct Biol 1997, 4:644-649. The solution structure of the theophylline aptamer reveals how several tertiary structure motifs collaborate to form a high-affinity, high-specificity binding site. The binding site is largely unstructured in the absence of bound ligand.
16. Cole PE, Yang SK, Crothers DM: Conformational changes of transfer ribonucleic acid. Equilibrium phase diagrams. Biochemistry 1972, 11:4358-4368.
17. Lynch DC, Schimmel PR: Cooperative binding of magnesium to transfer ribonucleic acid studied by a fluorescent probe. Biochemistry 1974, 13:1841-1852.
18. Wu M, Tinoco I: RNA folding causes secondary structure rearrangement. Proc Natl Acad Sci USA 1998, 95:11555-11560. NMR studies reveal that the secondary structure of a three-way junction from the Tetrahymena ribozyme rearranges at 15 positions upon tertiary structure formation. These results are inconsistent with a purely hierarchical folding mechanism and demonstrate that secondary and tertiary folding can be coupled.
19. 2+ ions in the P5abc three-way junction of the P4-P6 domain from the Tetrahymena ribozyme. Domain folding was eliminated by single-atom substitutions at positions of metal binding, indicating that the magnesium core is a folding nucleus. Possible parallels to hydrophobic cores in proteins are discussed.
20. Weeks KM, Cech TR: Assembly of a ribonucleoprotein catalyst by tertiary structure capture. Science 1996, 271:345-348.
21. -1), whereas the other half of the catalytic core, the P3-P7 domain, folds on the minute timescale.
22. Thirumalai D: Native secondary structure formation in RNA may be a slave to tertiary folding. Proc Natl Acad Sci USA 1998, 95:11506-11508. A thoughtful commentary on the theoretical implications of the findings of Wu and Tinoco [18••].
23. 2+ binding induce similar changes in the interhelical angles of a three-way junction in 16S rRNA.
24. Miick SM, Fee RS, Millar DP, Chazin WJ: Crossover isomer bias is the primary sequence-dependent property of immobilized holliday junctions. Proc Natl Acad Sci USA 1997, 94:9080-9084.
25. Grainger RJ, Murchie AIH, Lilley DMJ: Exchange between stacking conformers in a four-way DNA junction. Biochemistry 1998, 37:23-32.
26. Batey RT, Williamson JR: Effects of polyvalent cations on the folding of an rRNA three-way junction and binding of ribosomal protein S15. RNA 1998, 4:984-997. The presence of polyvalent cations dramatically increases the rate of S15 binding by pre-organizing the structure of a three-way junction from 16S rRNA (see [23•]). In the absence of ions, the pre-organized junction conformation is largely unpopulated and S15 binds slowly (minutes) by a 'tertiary structure capture' mechanism.
27. 2+ binding can be rate limiting. The authors make important comparisons with large ribozyme folding.
28. Treiber DK, Rook MS, Zarrinkar PP, Williamson JR: Kinetic intermediates trapped by native interactions in RNA folding. Science 1998, 279:1943-1946. The results of an in vitro selection study suggest that the formation rate of the P3-P7 domain in the Tetrahymena ribozyme is limited by escape from a kinetic trap that is stabilized by native interactions within the P4-P6 domain.
29. Pan T, Fang X, Sosnick T: Pathway modulation, circular permutation and rapid RNA folding under kinetic control. J Mol Biol 1999, 286:721-731. Circular permutation of the ribozyme from RNase P accelerates folding by preventing the formation of a previously identified kinetic trap [4•]. The folding pathway of the permuted molecule is also changed and is under kinetic control, whereby the least stable domain folds most rapidly. Most importantly, the results highlight the utility of engineered ribozymes that avoid kinetic traps in studying the fundamental aspects of RNA folding.
30. Batey RT, Doudna JA: The parallel universe of RNA folding. Nat Struct Biol 1998, 5:337-340. A thoughtful commentary on the findings presented in [21••,28••].
31. Downs WD, Cech TR: Kinetic pathway for folding of the tetrahymena ribozyme revealed by three UV-inducible cross-links. RNA 1996, 2:718-732.
32. Sclavi B, Woodson S, Sullivan M, Chance MR, Brenowitz M: Time-resolved synchrotron X-ray 'footprinting', a new approach to the study of nucleic acid structure and function: Applications to protein-dna interactions and RNA folding. J Mol Biol 1997, 266:144-159. In an important technical breakthrough, hydroxyl radical footprinting was developed as a rapid quench assay in order to monitor the kinetics of RNA folding with nucleotide resolution (see [21••]). Hydroxyl radicals are produced rapidly by brief exposure (50-100 ms) to high flux X-ray beams from a synchrotron source.
33. Szewczak AA, Cech TR: An RNA internal loop acts as a hinge to facilitate ribozyme folding and catalysis. RNA 1997, 3:838-849. The role of some elements in large RNAs is to simply remain unstructured. The internal loop that acts as a flexible hinge in the P4-P6 domain of the Tetrahymena ribozyme works best when unstructured in the unfolded state.
34. Cate JH, Gooding AR, Podell E, Zhou K, Golden BL, Kundrot CE, Cech TR, Doudna JA: Crystal structure of a group I ribozyme domain: Principles of RNA packing. Science 1996, 273:1678-1685.
35. Butcher SL, Dieckmann T, Feigon J: Solution structure of a GAAA tetraloop receptor RNA. EMBO J 1997, 16:7490-7499. The structure of the unbound GAAA tetraloop receptor (a base zipper) is different from the bound structure observed in the P4-P6 domain crystal structure (an adenosine platform). The receptor is thus not pre-organized for tetraloop binding and may rearrange by an induced-fit mechanism that involves initial docking with G·C pairs above the loop.
36. Szewczak AA, Podell ER, Bevilacqua PC, Cech TR: Thermodynamic stability of the P4-P6 domain RNA tertiary structure measured by temperature gradient gel electrophoresis. Biochemistry 1998, 37:11162-11170. Tertiary folding of the isolated P4-P6 domain from the Tetrahymena ribozyme is enthalpically driven, suggesting an important role for base stacking and hydrogen bonding. This contrasts with the docking of the substrate helix, which is entropically driven.
37. Doherty EA, Doudna JA: The P4-P6 domain directs higher order folding of the tetrahymena ribozyme core. Biochemistry 1997, 36:3159-3169. The P3-P7 domain from the Tetrahymena ribozyme, unlike the P4-P6 domain, can not form its native tertiary structure in isolation and packing interactions with P4-P6 are required for folding. Conformational searching in P3-P7 and subsequent 'capture' of the native structure by P4-P6 is likely to be a fundamental process that limits ribozyme folding.
38. Golden BL, Gooding AR, Podell ER, Cech TR: A preorganized active site in the crystal structure of the tetrahymena ribozyme. Science 1998, 282:259-264. A 5.0 Å crystal structure of a minimized version of the Tetrahymena ribozyme illustrates how the two structural domains pack together to form the active site.
39. Ortoleva-Donnelly L, Szewczak AA, Gutell RR, Strobel SA: The chemical basis for adenosine conservation throughout the tetrahymena ribozyme. RNA 1998, 4:498-519. The powerful Nucleotide Analog Interference Mapping (NAIM) method was used to generate biochemical constraints for structures involving adenosine within the Tetrahymena ribozyme.
40. Lehnert V, Jaeger L, Michel F, Westhof E: New loop-loop interactions in self-splicing introns of subgroup IC and ID: A complete 3D model of the tetrahymena thermophila ribozyme. Chem Biol 1996, 3:993-1009.
41. Zarrinkar PP, Wang J, Williamson JR: Slow folding kinetics of RNase P RNA. RNA 1996, 2:564-573.
42. Thirumalai D, Woodson SA: Kinetics of folding proteins and RNA. Accounts Chem Res 1996, 29:433-439.
43. d = 100 pM).
44. Basu S, Rambo RP, Strauss-Soukup J, Cate JH, Ferré-D'Amaré AR, Strobel SA, Doudna JA: A specific monovalent metal ion integral to the AA platform of the RNA tetraloop receptor. Nat Struct Biol 1998, 5:986-992. Divalent ions do not have a monopoly on specific binding sites in large RNAs. Crystallographic studies reveal a dehydrated potassium ion coordinated below the AA platform in the GAAA tetraloop receptor from the Tetrahymena ribozyme.
45. Draper DE, Misra VK: RNA shows its metal. Nat Struct Biol 1998, 5:927-930. A commentary on the finding that large ribozymes have specific binding sites for monovalent ions [44••]. A pedagogic discussion of the energetics involved in ion-RNA interactions follows.
46. Zhang F, Ramsay ES, Woodson SA: In vivo facilitation of tetrahymena group I intron splicing in escherichia coli preribosomal RNA. RNA 1995, 1:284-292.
47. Semrad K, Schroeder R: A ribosomal function is necessary for efficient splicing of the T4 phage thymidylate synthase intron in vivo. Genes Dev 1998, 12:1327-1337. The misfolding of large ribozymes occurs in vivo. Splicing of a group I intron is inefficient when uncoupled from translation in vivo, suggesting that the ribosome melts misfolded structures. RNA-binding proteins that have chaperone activity or that stabilize native structure restore efficient splicing.