Stability of XGCGCp, GCGCYp, and XGCGCYp helixes: an empirical estimate of the energetics of hydrogen bonds in nucleic acids

Freier, Susan M.; Sugimoto, Naoki; Sinclair, Alison; Alkema, Dirk; Neilson, Thomas; Kierzek, Ryszard; Caruthers, Marvin H.; Turner, Douglas H.

doi:10.1021/bi00359a020

Cited by 135 publications

(172 citation statements)

References 39 publications

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“…3′-G--5′ overhang stabilizes the duplex by 1.8 kcal/mol, while the 5′-GA-3′ 3′-C--5′ overhang only stabilizes the same duplex by 1.1 kcal/mol (31).…”

Section: Resultsmentioning

confidence: 98%

“…3′-G--5′ overhang stabilizes the duplex by 1.7 kcal/mol, while the 5′-CU-3′ 3′-G--5′ overhang only stabilizes the same duplex by 1.2 kcal/mol (31). It has also been shown that by appropriately attaching multiring fused systems [4-desmethylwyosine (39), quinolones (38), phenazinium (51,52), pyrene and phenanthrene (42), phenylurea and naphthylurea (41), cholic acid (53, 54) and a 5′-acylamido FIGURE 2: Definition of the distances used to calculate the hydrogen bond screening value.…”

Section: Resultsmentioning

confidence: 99%

“…(3) Perhaps the most important obserVation is that the nature of the closing basepair plays a central role (29)(30)(31)(32)(33)(34). The same dangling nucleobase stacking on a G-C closing basepair with three hydrogen bonds always provides more stabilization than the A-U closing basepair with two hydrogen bonds.…”

Section: Resultsmentioning

confidence: 99%

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A Uniform Mechanism Correlating Dangling-End Stabilization and Stacking Geometry

Isaksson

Chattopadhyaya

2005

Biochemistry

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The geometry of the dangling base in 105 published structures (from X-ray/NMR) containing single-stranded overhangs has been analyzed and correlated to the thermodynamic stabilization found (UV) for the corresponding dangling base/closing basepair combination in short oligonucleotides. The study considers most combinations of closing basepairs, sequence and dangling base residue type, attached in both the 3′-and 5′-ends of both DNA and RNA. Linear regression analysis showed a straightforward correlation (R ) 0.873) between the degree of screening for the hydrogen bonds of the closing basepair provided by the dangling base and the resulting thermodynamic stabilization in both DNA and RNA series with dangling ends either at the 3′-or at the 5′-terminus. Regression analysis of only the datasets from RNA gives an improved correlation, R ) 0.934, showing that dangling ends on RNA are more ordered than the dangling ends on DNA, R ) 0.376. This study highlights the gain in the free energy of stabilization owing to the favorable stacking between the dangling nucleobase and the neighboring basepair and the resulting strengthening of the hydrogen bond of the closing basepair. By acting as a hydrophobic cap on the terminal of the DNA or RNA duplex, the dangling-end residue restricts the bulk water access to the terminal basepair, thereby providing it with a microenvironment devoid of water, which consequently enhances its thermodynamic stability, making it energetically comparable to the corresponding internal basepair. Thus, one single structural model consisting of the interplay of the above electrostatic interactions can be used to explain the molecular basis of the observed thermodynamic effects for dangling-end attachment to the 3′-and 5′-ends of both DNA and RNA duplexes, which is a key step toward accurate dangling-end effect prediction.Unpaired terminal nucleotides naturally occur in various biologically important RNA structures: The acceptor stem in tRNA (1-3) has a characteristic 3′-NCCA nucleobase overhang that determines its structure, stability, and function. The dangling ends neighboring the codon-anticodon pair have also been found to stabilize the interaction between tRNA and mRNA (4, 5) for protein synthesis in the ribosomal machinery. The efficiency of down regulation of gene expression by RNA interference (RNAi) has been shown to be dependent on a two to three nucleotide overhang (6-9). Similarly, the structures of pseudoknots (10) are stabilized by a complicated interplay between single-stranded and double-stranded motifs. A multitude of literature on the stabilizing interactions of native single-stranded oligonucleotides is available (9,(11)(12)(13)(14).Accurate prediction of nucleic acid secondary structure and stability from its primary sequence is a key interest for probe binding optimization in biotechnological applications such as microarrays (15) and molecular beacons (16). To develop an accurate algorithm (14,(17)(18)(19)(20)(21)(22)(23)(24) for predicting the thermodynamics of hybridi...

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“…3′-G--5′ overhang stabilizes the duplex by 1.8 kcal/mol, while the 5′-GA-3′ 3′-C--5′ overhang only stabilizes the same duplex by 1.1 kcal/mol (31).…”

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

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A Uniform Mechanism Correlating Dangling-End Stabilization and Stacking Geometry

Isaksson

Chattopadhyaya

2005

Biochemistry

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“…A,G . C; Tables 2, 3) does not correspond to energetic values measured for base-stacking+ Turner and co-workers measured the free energy of base-stacking for 39-dangling ends and found that purines contributed 0+4-1+0 kcal/mol more than did pyrimidines (Freier et al+, 1986b)+ Calculations of base-stacking free energies for ribodinucleoside monophosphates also suggested a preference for the purine-purine interaction (Norberg & Nilsson, 1995)+ That these trends are not reflected in the data presented in this work suggests that the long-range displacements necessary for crosslinking of duplexes separated by a gap require overcoming an energetic barrier greater than the barrier to disrupt base-stacking+…”

Section: Comparison Of Data With Previous Studiesmentioning

confidence: 93%

A quantitative study of the flexibility contributed to RNA structures by nicks and single-stranded gaps

Cohen¹,

Cech²

1998

RNA

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Disulfide crosslinking via thiol-disulfide interchange was applied to quantitate the relative flexibility contributed by nicks and single-stranded gaps in an RNA structure. An RNA duplex comprised of three strands was constructed containing the disulfide crosslink precursors 1 and 2 at opposite ends of the duplex on opposite strands. The third strand was of varying length to yield a nick or single-stranded gaps of 1, 2, or 3 nt. Crosslinking rates indicated relative flexibilities of the resulting two-helix junctions. Crosslinking in the nicked duplex occurred two orders of magnitude slower than in a duplex containing a 3-nt gap. Rates of crosslinking in duplexes with 3-and 2-nt gaps showed only modest dependence on the gap sequence. Many natural RNAs, including ribozymes, contain two-helix junctions related to the model system described here. The data suggest that two-helix junctions containing a nick in one strand will retain substantial rigidity, whereas one or more single-stranded nucleotides at a two-helix junction allow significant flexibility.

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“…Second, mutating As7 or Ags to a pyrimidine (U, C) is more detrimental than mutating it to another purine (G). Pyrimidines typically do not contribute as much energetically to stacking interactions as purines (Saenger 1984;Freier et al 1986). Therefore, this second observation is consistent with As7 and Ags participating in one or more stacking interactions.…”

Section: Asz and Ags Contribute Structural Stabilitymentioning

confidence: 99%

A tertiary interaction in the Tetrahymena intron contributes to selection of the 5' splice site.

Downs¹,

Cech²

1994

Genes Dev.

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The utilization of cryptic splice sites has been observed in a number of RNA splicing reactions. In the self-splicing group I intron of Tetrahymena thermophila, point mutations of either As7 or A9s promote cleavage at two sites other than the normal 5' splice site, suggesting that these nucleotides are involved in a common tertiary interaction. These results are unusual since As7 and A9s are neither at nor near the 5' splice site in the sequence or secondary structure. Cleavage at the alternative sites appears to occur by intron cyclization, a reaction with well-established structural and mechanistic similarities to the first step of RNA self-splicing. Alternative docking of Pl (the helix containing the 5' splice site paired to the internal guide sequence of the intron) into the catalytic core accounts for cleavage at the cryptic reaction sites. We propose that the AsT/A9s interaction, along with an element implicated previously (J1/2), provide structural connectivity from the reaction site in Pl to the catalytic core of the Tetrahymena intron. It seems likely that RNA splicing in general will require such tertiary interactions to position RNA helices.[Key Words: Accuracy; group I introns; photo-cross-linking; ribozyme; RNA splicing; RNA tertiary structure] Received March 11, 1994; revised version accepted April 12, 1994.In spliceosomal mRNA splicing and in self-splicing, RNA makes up part or all of the splicing machinery. In each case, the first chemical step is cleavage at the 5' splice site, a reaction that must occur with high accuracy. Our understanding of 5' splice site selection has focused on base-pairing interactions, and in each case RNA components of the splicing machinery have been found to provide binding sites or "guide sequences" that base-pair with sequence flanking the 5' splice site. In group I and group II self-splicing reactions, the introns themselves provide the base-pairing sequences (Davies et al. 1982;Michel and Dujon 1983;Michel et al. 1989b). In nuclear mRNA splicing the initial recognition is by the U1 small nuclear RNA (snRNA} (Lerner et al. 1980;Zhuang and Weiner 1986;Guthrie 1991), later to be replaced by base-pairing with U5 and U6 snRNAs (Kandels-Lewis and S6raphin 1993; Lesser and Guthrie 1993; Sontheimer and Steitz 1993). Whereas these base-pairing interactions are necessary to direct the first step of splicing, it seems unlikely that they alone could ensure accuracy; once the splice-site duplex is formed, some mechanism is needed to align it with respect to the attacking group, which is contained in a second RNA du- plex (P7 in group I introns, domain VI in group II introns, the U2 snRNA, branch site duplex in nuclear mRNA introns). We now identify a tertiary interaction in the Tetrahymena group I intron that helps to provide this next level of accuracy by holding the 5' splice-site duplex into the proper position for splicing.Self-splicing of the Tetrahymena pre-rRNA and cyclization of the excised intron occur in three steps, each involving the same chemical mechanism of tran...

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Stability of XGCGCp, GCGCYp, and XGCGCYp helixes: an empirical estimate of the energetics of hydrogen bonds in nucleic acids

Cited by 135 publications

References 39 publications

A Uniform Mechanism Correlating Dangling-End Stabilization and Stacking Geometry

A Uniform Mechanism Correlating Dangling-End Stabilization and Stacking Geometry

A quantitative study of the flexibility contributed to RNA structures by nicks and single-stranded gaps

A tertiary interaction in the Tetrahymena intron contributes to selection of the 5' splice site.

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