RNA seeing double: Close-packing of helices in RNA tertiary structure

Strobel, Scott A.; Doudna, Jennifer A.

doi:10.1016/s0968-0004(97)01056-6

Cited by 45 publications

(27 citation statements)

References 45 publications

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“…The Tetrahymena ribozyme, derived from a selfsplicing group I intron, has served as a valuable model system for understanding how an RNA molecule can achieve and maintain a discrete three-dimensional structure (for recent reviews, see Strobel & Doudna, 1997;Brion & Westhof, 1997). The ribozyme is composed of a conserved catalytic core, containing the paired structural elements P4, P5, P6 and P3-P7-P8, and additional peripheral elements that are conserved among members of intron subclasses (Figure 1(a)).…”

Section: Introductionmentioning

confidence: 99%

New pathways in folding of the Tetrahymena group I RNA enzyme

Russell

Herschlag

1999

Journal of Molecular Biology

103

149

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Section: Introductionmentioning

confidence: 99%

New pathways in folding of the Tetrahymena group I RNA enzyme

Russell

Herschlag

1999

Journal of Molecular Biology

103

149

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“…The structures of complex RNAs show that regulatory, structural, and catalytic RNAs adopt well-defined globular or tertiary structures where secondary structural units (helices) pack against one another (see Strobel and Doudna, 1997, for a review)+ These higher-order structures are stabilized by helix-helix stacking interactions in the formation of 2, 3, and 4-helix junctions and by helix-single-stranded loop and loop-loop interactions, some of which are stabilized or mediated by divalent cations+ An RNA pseudoknot constitutes one of the simplest RNA folding motifs containing a twohelix junction+ Pseudoknots play fundamental roles in structurally organizing complex RNAs, and in translational regulation where they modulate ribosome loading and stimulate translational recoding or frameshifting within the coding regions of mRNAs (Atkins & Gesteland, 1999)+ For example, hairpin-type (H-type) RNA pseudoknots stimulate ribosomal frameshifting when they are positioned 39 to an mRNA slippery sequence (Chamorro et al+, 1992), although the precise mechanism remains undefined+ An H-type pseudoknot consists of an RNA hairpin that forms the 59 helical stem of the pseudoknot (stem 1) and the first loop of the pseudoknot (loop 1)+ This is followed by a single-stranded region that forms the second loop of the pseudoknot (loop 2) and a region complementary to part of the hairpin loop sequence, which forms the second helical stem of the pseudoknot (stem 2) (Fig+ 1)+ The helical stems can be coaxially stacked and nearly colinear Hol-land et al+, 1999) or strongly bent Su et al+, 1999)+…”

Section: Introductionmentioning

confidence: 99%

Contribution of the intercalated adenosine at the helical junction to the stability of the gag-pro frameshifting pseudoknot from mouse mammary tumor virus

Theimer

Giedroc

2000

RNA

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The mouse mammary tumor virus (MMTV) gag-pro frameshifting pseudoknot is an H-type RNA pseudoknot that contains an unpaired adenosine (A14) at the junction of the two helical stems required for efficient frameshifting activity. The thermodynamics of folding of the MMTV vpk pseudoknot have been compared with a structurally homologous mutant RNA containing a G•U to G-C substitution at the helical junction (U13C RNA), and an A14 deletion mutation in that context (U13CDA14 RNA). Dual wavelength optical melting and differential scanning calorimetry reveal that the unpaired adenosine contributes 0.7 (60.2) kcal mol -1 at low salt and 1.4 (60.2) kcal mol -1 to the stability (DG8 37 ) at 1 M NaCl. This stability increment derives from a favorable enthalpy contribution to the stability DDH 5 6.6 (62.1) kcal mol -1 with DDG8 37 comparable to that predicted for the stacking of a dangling 39 unpaired adenosine on a G-C or G•U base pair. Group 1A monovalent ions, NH 4 1 , Mg 21 , and Co(NH 3 ) 6 31 ions stabilize the A14 and DA14 pseudoknots to largely identical extents, revealing that the observed differences in stability in these molecules do not derive from a differential or specific accumulation of ions in the A14 versus DA14 pseudoknots. Knowledge of this free energy contribution may facilitate the prediction of RNA pseudoknot formation from primary nucleotide sequence (Gultyaev et al., 1999, RNA 5:609-617).

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“…Sci. USA 95 (1998)natural or artificial, that makes use of an extended triple helix for the formation of its active structure (22). Targeted Cleavage of DNA Restriction Sites with Deoxyribozymes.…”

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confidence: 99%

Cleaving DNA with DNA

Carmi

Balkhi

Breaker

1998

Proc. Natl. Acad. Sci. U.S.A.

238

165

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A DNA structure is described that can cleave single-stranded DNA oligonucleotides in the presence of ionic copper. This ''deoxyribozyme'' can self-cleave or can operate as a bimolecular complex that simultaneously makes use of duplex and triplex interactions to bind and cleave separate DNA substrates. Bimolecular deoxyribozyme-mediated strand scission proceeds with a k obs of 0.2 min ؊1 , whereas the corresponding uncatalyzed reaction could not be detected. The duplex and triplex recognition domains can be altered, making possible the targeted cleavage of single-stranded DNAs with different nucleotide sequences. Several small synthetic DNAs were made to function as simple ''restriction enzymes'' for the site-specific cleavage of single-stranded DNA.DNA in biological systems exists primarily in duplex form where it serves almost exclusively as a storage system for genetic information. Outside the confines of cells, DNA in its single-stranded form can be made to perform both molecular recognition and catalysis-biochemical operations that were until recently thought to be possible only with macromolecules made of protein or RNA. For example, a number of DNA ''aptamers'' (1) can be made that function as ligands for proteins or as highly specific receptors for small organic molecules (2-4). In addition, certain single-stranded DNAs act as artificial enzymes (4-6), catalyzing such chemical reactions as phosphoester transfer (7-12), phosphoester formation (13), porphyrin metalation (14), phosphoramidate cleavage (15), and DNA cleavage (16). Most likely, DNA can be made to perform a much broader repertoire of catalytic activities (6).These capabilities of DNA conceivably can be exploited to create a variety of structured DNAs that perform useful tasks, either in vitro or in vivo, involving molecular recognition and catalysis. Such functional DNAs offer several advantages, including ease of synthesis and chemical stability, that might make attractive properties for polymers that serve as artificial receptors or as biocatalysts for various applications. Characteristics such as thermostability and solvent͞solute preferences could be conferred upon deoxyribozymes by using both rational and combinatorial methods of molecular design. Catalytic DNAs may offer distinct advantages over natural protein enzymes for operation under nonbiological conditions.In a previous study (16), we reported the isolation of two distinct types of deoxyribozymes (classes I and II) that undergo oxidative self-cleavage in the presence of copper ions. By using in vitro selection (17), class II self-cleaving DNAs have been further optimized for catalytic function, and the most active structure obtained from this process has been engineered to act as a ''restriction endonuclease'' for single-stranded DNA substrates. MATERIALS AND METHODSOligonucleotides. Synthetic DNAs were prepared by automated chemical synthesis (Keck Biotechnology Resource Laboratory, Yale University) and were purified by denaturing (8 M urea) PAGE prior to use. Double-stran...

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RNA seeing double: Close-packing of helices in RNA tertiary structure

Cited by 45 publications

References 45 publications

New pathways in folding of the Tetrahymena group I RNA enzyme

New pathways in folding of the Tetrahymena group I RNA enzyme

Contribution of the intercalated adenosine at the helical junction to the stability of the gag-pro frameshifting pseudoknot from mouse mammary tumor virus

Cleaving DNA with DNA

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