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An RNA folding motif: GNRA tetraloop–receptor interactions

  • Julie L. Fiore (a1) and David J. Nesbitt (a1)
Abstract
Abstract

Nearly two decades after Westhof and Michel first proposed that RNA tetraloops may interact with distal helices, tetraloop–receptor interactions have been recognized as ubiquitous elements of RNA tertiary structure. The unique architecture of GNRA tetraloops (N=any nucleotide, R=purine) enables interaction with a variety of receptors, e.g., helical minor grooves and asymmetric internal loops. The most common example of the latter is the GAAA tetraloop–11 nt tetraloop receptor motif. Biophysical characterization of this motif provided evidence for the modularity of RNA structure, with applications spanning improved crystallization methods to RNA tectonics. In this review, we identify and compare types of GNRA tetraloop–receptor interactions. Then we explore the abundance of structural, kinetic, and thermodynamic information on the frequently occurring and most widely studied GAAA tetraloop–11 nt receptor motif. Studies of this interaction have revealed powerful paradigms for structural assembly of RNA, as well as providing new insights into the roles of cations, transition states and protein chaperones in RNA folding pathways. However, further research will clearly be necessary to characterize other tetraloop–receptor and long-range tertiary binding interactions in detail – an important milestone in the quantitative prediction of free energy landscapes for RNA folding.

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*Author for Correspondence: D. J. Nesbitt, JILA, National Institute of Standards and Technology, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA. Tel.: (303)492-8857; Fax: (303)492-5235; E-mail: djn@jila.colorado.edu
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

D. L. Abramovitz & A. M. Pyle (1997). Remarkable morphological variability of a common RNA folding motif: the GNRA tetraloop–receptor interaction. Journal of Molecular Biology 266, 493506.

P. L. Adams , M. R. Stahley , A. B. Kosek , J. M. Wang & S. A. Strobel (2004b). Crystal structure of a self-splicing group I intron with both exons. Nature 430, 4550.

V. P. Antao & I. Tinoco (1992). Thermodynamic parameters for loop formation in RNA and DNA hairpin tetraloops. Nucleic Acids Research 20, 819824.

V. P. Antao , S. Y. Lai & I. Tinoco (1991). A thermodynamic study of unusually stable RNA and DNA hairpins. Nucleic Acids Research 19, 59015905.

N. J. Baird , E. Westhof , H. Qin , T. Pan & T. R. Sosnick (2005). Structure of a folding intermediate reveals the interplay between core and peripheral elements in RNA folding. Journal of Molecular Biology 352, 712722.

T. L. Benz-Moy & D. Herschlag (2011). Structure-function analysis from the outside in: long-range tertiary contacts in RNA exhibit distinct catalytic roles. Biochemistry 50, 87338755.

G. Bokinsky , D. Rueda , V. K. Misra , M. M. Rhodes , A. Gordus , H. P. Babcock , N. G. Walter & X. W. Zhuang (2003). Single-molecule transition-state analysis of RNA folding. Proceedings of the National Academy of Sciences, USA 100, 93029307.

P. Brion & E. Westhof (1997). Hierarchy and dynamics of RNA folding. Annual Review of Biophysics and Biomolecular Structure 26, 113137.

J. W. Brown , J. M. Nolan , E. S. Haas , M. A. T. Rubio , F. Major & N. R. Pace (1996). Comparative analysis of ribonuclease P RNA using gene sequences from natural microbial populations reveals tertiary structural elements. Proceedings of the National Academy of Sciences, USA 93, 30013006.

S. E. Butcher & A. M. Pyle (2011). The molecular interactions that stabilize RNA tertiary structure: RNA motifs, patterns, and networks. Accounts of Chemical Research 44, 13021311.

S. E. Butcher , T. Dieckmann & J. Feigon (1997). Solution structure of a GAAA tetraloop receptor RNA. EMBO Journal 16, 74907499.

C. C. Correll & K. Swinger (2003). Common and distinctive features of GNRA tetraloops based on a GUAA tetraloop structure at 1.4 angstrom resolution. RNA 9, 355363.

C. C. Correll , A. Munishkin , Y. L. Chan , Z. Ren , I. G. Wool & T. A. Steitz (1998). Crystal structure of the ribosomal RNA domain essential for binding elongation factors. Proceedings of the National Academy of Sciences, USA 95, 1343613441.

M. Costa & F. Michel (1997). Rules for RNA recognition of GNRA tetraloops deduced by in vitro selection: comparison with in vivo evolution. EMBO Journal 16, 32893302.

E. A. Doherty , R. T. Batey , B. Masquida & J. A. Doudna (2001). A universal mode of helix packing in RNA. Nature Structural Biology 8, 339343.

C. D. Downey , J. L. Fiore , C. D. Stoddard , J. H. Hodak , D. J. Nesbitt & A. Pardi (2006). Metal ion dependence, thermodynamics, and kinetics for intramolecular docking of a GAAA tetraloop and receptor connected by a flexible linker. Biochemistry 45, 36643673.

A. Fedoruk-Wyszomirska , M. Szymanski , E. Wyszko , M. Z. Barciszewska & J. Barciszewski (2009). Highly active low magnesium hammerhead ribozyme. Journal of Biochemistry 145, 451459.

J. L. Fiore , J. H. Hodak , O. Piestert , C. D. Downey & D. J. Nesbitt (2008). Monovalent and divalent promoted GAAA tetraloop-receptor tertiary interactions from freely diffusing single-molecule studies. Biophysical Journal 95, 38923905.

Y. Fujita , T. Tanaka , H. Furuta & Y. Ikawa (2012). Functional roles of a tetraloop/receptor interacting module in a cyclic di-GMP riboswitch. Journal of Bioscience and Bioengineering 113, 141145.

C. Geary , S. Baudrey & L. Jaeger (2008). Comprehensive features of natural and in vitro selected GNRA tetraloop-binding receptors. Nucleic Acids Research 36, 11381152.

M. Greenfeld , S. V. Solomatin & D. Herschlag (2011). Removal of covalent heterogeneity reveals simple folding behavior for P4-P6 RNA. Journal of Biological Chemistry 286, 1987219879.

P. Hanggi , P. Talkner & M. Borkovec (1990). Reaction-rate theory: 50 years after Kramers. Reviews of Modern Physics 62, 251341.

E. D. Holmstrom , J. L. Fiore & D. J. Nesbitt (2012). Thermodynamic origins of monovalent-facilitated RNA folding. Biochemistry 51, 37323743.

Y. Ikawa , K. Fukada , S. Watanabe , H. Shiraishi & T. Inoue (2002). Design, construction, and analysis of a novel class of self-folding RNA. Structure 10, 527534.

L. Jaeger & N. B. Leontis (2000). Tecto-RNA: one-dimensional self-assembly through tertiary interactions. Angewandte Chemie-International Edition 39, 25212524.

L. Jaeger , F. Michel & E. Westhof (1994). Involvement of a GNRA tetraloop in long-range tertiary interactions. Journal of Molecular Biology 236, 12711276.

K. Juneau , E. Podell , D. J. Harrington & T. R. Cech (2001). Structural basis of the enhanced stability of a mutant ribozyme domain and a detailed view of RNA-solvent interactions. Structure 9, 221231.

K. S. Keating , N. Toor & A. M. Pyle (2008). The GANC Tetraloop: a novel Motif in the group IIC intron structure. Journal of Molecular Biology 383, 475481.

P. S. Klosterman , D. K. Hendrix , M. Tamura , S. R. Holbrook & S. E. Brenner (2004). Three-dimensional motifs from the SCOR, structural classification of RNA database: extruded strands, base triples, tetraloops and U-turns. Nucleic Acids Research 32, 23422352.

A. S. Krasilnikov , X. J. Yang , T. Pan & A. Mondragon (2003). Crystal structure of the specificity domain of ribonuclease P. Nature 421, 760764.

N. Kulshina , N. J. Baird & A. R. Ferre-D'amare (2009). Recognition of the bacterial second messenger cyclic diguanylate by its cognate riboswitch. Nature Structural and Molecular Biology 16, 12121217.

D. Lambert , D. Leipply , R. Shiman & D. E. Draper (2009). The influence of monovalent cation size on the stability of RNA tertiary structures. Journal of Molecular Biology 390, 791804.

J. C. Lee , R. R. Gutell & R. Russell (2006). The UAA/GAN internal loop motif: a new RNA structural element that forms a cross-strand AAA stack and long-range tertiary interactions. Journal of Molecular Biology 360, 978988.

F. Michel , M. Hanna , R. Green , D. P. Bartel & J. W. Szostak (1989). The guanosine binding-Site of the Tetrahymena ribozyme. Nature 342, 391395.

V. K. Misra & D. E. Draper (2001). A thermodynamic framework for Mg2+ binding to RNA. Proceedings of the National Academy of Sciences, USA 98, 1245612461.

I. V. Novikova , B. H. Hassan , M. G. Mirzoyan & N. B. Leontis (2011). Engineering cooperative tecto-RNA complexes having programmable stoichiometries. Nucleic Acids Research 39, 29032917.

H. W. Pley , K. M. Flaherty & D. B. Mckay (1994b). Model for an RNA tertiary interaction from the structure of an intermolecular complex between a GAAA tetraloop and an RNA helix. Nature 372, 111113.

G. Pljevaljcic , D. P. Millar & A. A. Deniz (2004). Freely diffusing single hairpin ribozymes provide insights into the role of secondary structure and partially folded states in RNA folding. Biophysical Journal 87, 457467.

D. J. Proctor , J. E. Schaak , J. M. Bevilacqua , C. J. Falzone & P. C. Bevilacqua (2002). Isolation and characterization of a family of stable RNA tetraloops with the motif YNMG that participate in tertiary interactions. Biochemistry 41, 1206212075.

P. Z. Qin , J. Feigon & W. L. Hubbell (2005). Site-directed spin labeling studies reveal solution conformational changes in a GAAA tetraloop receptor upon Mg2+-dependent docking of a GAAA tetraloop. Journal of Molecular Biology 351, 18.

R. Ramos & E. Martinez-Salas (1999). Long-range RNA interactions between structural domains of the aphthovirus internal ribosome entry site (IRES). RNA 5, 13741383.

E. E. Regulski , R. H. Moy , Z. Weinberg , J. E. Barrick , Z. Yao , W. L. Ruzzo & R. R. Breaker (2008). A widespread riboswitch candidate that controls bacterial genes involved in molybdenum cofactor and tungsten cofactor metabolism. Molecular Microbiology 68, 918932.

N. J. Reiter , A. Osterman , A. Torres-Larios , K. K. Swinger , T. Pan & A. Mondragon (2010). Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA. Nature 468, 784789.

J. Santalucia , R. Kierzek & D. H. Turner (1992). Context dependence of hydrogen-bond free-energy revealed by substitutions in an RNA hairpin. Science 256, 217219.

T. Shiohara , H. Saito & T. Inoue (2009). A designed RNA selection: establishment of a stable complex between a target and selectant RNA via two coordinated interactions. Nucleic Acids Research 37, e23.

S. K. Silverman & T. R. Cech (2001). An early transition state for folding of the P4-P6 RNA domain. RNA 7, 161166.

N. Sudarsan , E. R. Lee , Z. Weinberg , R. H. Moy , J. N. Kim , K. H. Link & R. R. Breaker (2008). Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science 321, 411413.

A. A. Szewczak , E. R. Podell , P. C. Bevilacqua & T. R. Cech (1998). Thermodynamic stability of the P4-P6 domain RNA tertiary structure measured by temperature gradient gel electrophoresis. Biochemistry 37, 1116211170.

M. Tamura & S. R. Holbrook (2002). Sequence and structural conservation in RNA ribose zippers. Journal of Molecular Biology 320, 455474.

E. Tan , T. J. Wilson , M. K. Nahas , R. M. Clegg , D. M. J. Lilley & T. Ha (2003). A four-way junction accelerates hairpin ribozyme folding via a discrete intermediate. Proceedings of the National Academy of Sciences, USA 100, 93089313.

N. Toor , K. S. Keating , S. D. Taylor & A. M. Pyle (2008). Crystal structure of a self-spliced group II intron. Science 320, 7782.

A. Torres-Larios , K. K. Swinger , T. Pan & A. Mondragon (2006). Structure of ribonuclease P – a universal ribozyme. Current Opinion in Structural Biology 16, 327335.

K. A. Vander Meulen & S. E. Butcher (2012). Characterization of the kinetic and thermodynamic landscape of RNA folding using a novel application of isothermal titration calorimetry. Nucleic Acids Research 40, 21402151.

K. A. Vander Meulen , J. H. Davis , T. R. Foster , T. Record & S. E. Butcher (2008). Thermodynamics and folding pathway of tetraloop receptor-mediated RNA helical packing. Journal of Molecular Biology 384, 702717.

V. Venditti , L. Clos , N. Niccolai & S. E. Butcher (2009). Minimum-energy path for a U6 RNA conformational change involving protonation, base-pair rearrangement and base flipping. Journal of Molecular Biology 391, 894905.

Y. X. Wang , X. B. Zuo , J. B. Wang , P. Yu & S. E. Butcher (2010). Rapid global structure determination of large RNA and RNA complexes using NMR and small-angle X-ray scattering. Methods 52, 180191.

E. Westhof , B. Masquida & L. Jaeger (1996). RNA tectonics: towards RNA design. Folding and Design 1, R78R88.

E. Westhof , B. Masquida & L. Jaeger (1998b). RNA tectonics and modular modeling of RNA. In Molecular Modeling of Nucleic Acids. Washington, DC: American Chemical Society, vol. 682, pp. 346358.

W. C. Winkler & R. R. Breaker (2005). Regulation of bacterial gene expression by riboswitches. Annual Review of Microbiology 59, 487517.

C. R. Woese , S. Winker & R. R. Gutell (1990). Architecture of ribosomal-RNA: constraints on the sequence of Tetra-loops. Proceedings of the National Academy of Sciences, USA 87, 84678471.

Y. R. Xin , C. Laing , N. B. Leontis & T. Schlick (2008). Annotation of tertiary interactions in RNA structures reveals variations and correlations. RNA 14, 24652477.

Q. Zhao , H. C. Huang , U. Nagaswamy , Y. Xia , X. Gao & G. E. Fox (2012). UNAC tetraloops: to what extent do they mimic GNRA tetraloops?. Biopolymers 97 617628.

X. W. Zhuang , H. Kim , M. J. B. Pereira , H. P. Babcock , N. G. Walter & S. Chu (2002). Correlating structural dynamics and function in single ribozyme molecules. Science 296, 14731476.

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