Solution structure of a modified 2',5'-linked RNA hairpin involved in an equilibrium with duplex

Plevnik, Miha; Gdaniec, Zofia; Plavec, Janez

doi:10.1093/nar/gki318

Cited by 10 publications

(5 citation statements)

References 40 publications

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“…The pure RNA version of Dickerson sequence also adopts a duplex structure in solution ( 48 ). However, several modifications in the RNA sequence have been reported to induce hairpin formation ( 49–51 ).…”

Section: Discussionmentioning

confidence: 99%

The solution structure of double helical arabino nucleic acids (ANA and 2′F-ANA): effect of arabinoses in duplex-hairpin interconversion

Martín-Pintado

Yahyaee-Anzahaee

Campos-Olivas

et al. 2012

Nucleic Acids Research

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We report here the first structure of double helical arabino nucleic acid (ANA), the C2′-stereoisomer of RNA, and the 2′-fluoro-ANA analogue (2′F-ANA). A chimeric dodecamer based on the Dickerson sequence, containing a contiguous central segment of arabino nucleotides, flanked by two 2′-deoxy-2′F-ANA wings was studied. Our data show that this chimeric oligonucleotide can adopt two different structures of comparable thermal stabilities. One structure is a monomeric hairpin in which the stem is formed by base paired 2′F-ANA nucleotides and the loop by unpaired ANA nucleotides. The second structure is a bimolecular duplex, with all the nucleotides (2′F-ANA and ANA) forming Watson–Crick base pairs. The duplex structure is canonical B-form, with all arabinoses adopting a pure C2′-endo conformation. In the ANA:ANA segment, steric interactions involving the 2′-OH substituent provoke slight changes in the glycosidic angles and, therefore, in the ANA:ANA base pair geometry. These distortions are not present in the 2′F-ANA:2′F-ANA regions of the duplex, where the –OH substituent is replaced by a smaller fluorine atom. 2′F-ANA nucleotides adopt the C2′-endo sugar pucker and fit very well into the geometry of B-form duplex, allowing for favourable 2′F···H8 interactions. This interaction shares many features of pseudo-hydrogen bonds previously observed in 2′F-ANA:RNA hybrids and in single 2′F-ANA nucleotides.

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Section: Discussionmentioning

confidence: 99%

The solution structure of double helical arabino nucleic acids (ANA and 2′F-ANA): effect of arabinoses in duplex-hairpin interconversion

Martín-Pintado

Yahyaee-Anzahaee

Campos-Olivas

et al. 2012

Nucleic Acids Research

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“…2′-modifications can influence the sugar conformation to adopt a predominantly North-type (N) sugar pucker, and can also improve properties such as affinity ( 20–24 ). 2′-modifications that provide a gauche effect and/or a charge effect can play a significant role in the level of nuclease resistance.…”

Section: Introductionmentioning

confidence: 99%

Solution-state structure of a fully alternately 2′-F/2′-OMe modified 42-nt dimeric siRNA construct

Podbevšek¹,

Allerson²,

Plavec³

2010

Nucleic Acids Research

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A high-resolution solution structure of a stable 42-nt RNA dimeric construct has been derived based on a high number of NMR observables including nuclear overhauser effects (NOEs), J-coupling constants and residual dipolar couplings (RDCs), which were all obtained with isotopically unlabeled molecules. Two 21-nt siRNA that efficiently hybridize consist of ribose units that were alternately substituted by 2′-fluoro or 2′-methoxy groups. Structure calculations utilized a set of H-F RDC values for all 21 2′-fluoro modified nucleotides under conditions of weak alignment achieved by Pf1 phages. A completely 2′-F/2′-OMe modified dimeric RNA construct adopts an antiparallel double-helical structure consisting of 19 Watson–Crick base pairs with additional 3′ UU overhangs and a 5′ phosphate group on the antisense strand. NMR data suggest that the stability of individual base pairs is not uniform throughout the construct. While most of the double helical segment exhibits well dispersed imino resonances, the last three base pairs either display uncharacteristic chemical shifts of imino protons or absence of imino resonances even at lower temperatures. Accessibility of imino protons to solvent exchange suggests a difference in stability of duplex ends, which might be of importance for incorporation of the guide siRNA strand into a RISC.

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“…2′,5′-Linked RNA is arguably the closest chemical analogue of native 3′,5′-linked RNA. However, the thermal stability and dynamics of duplexes formed by these two structural isomers are markedly different . Thus, we hypothesized that duplex 2′,5′ RNA would respond differently to intercalation in comparison to natural RNA and, therefore, represents an excellent model system for probing the role of backbone structure in the thermodynamics and ligand specificity of nucleic acid intercalation.…”

Section: Introductionmentioning

confidence: 99%

Solution Structure and Thermodynamics of 2′,5′ RNA Intercalation

et al. 2009

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As a means to explore the influence of the nucleic acid backbone on the intercalative binding of ligands to DNA and RNA, we have determined the solution structure of a proflavine-bound 2',5'-linked octamer duplex with the sequence GCCGCGGC. This structure represents the first NMR structure of an intercalated RNA duplex, of either backbone structural isomer. By comparison with X-ray crystal structures, we have identified similarities and differences between intercalated 3',5' and 2',5'-linked RNA duplexes. First, the two forms of RNA have different sugar pucker geometries at the intercalated nucleotide steps, yet have the same interphosphate distances. Second, as in intercalated 3',5' RNA, the phosphate backbone angle zeta at the 2',5' RNA intercalation site prefers to be in the trans conformation, whereas unintercalated 2',5' and 3',5' RNA prefer the -gauche conformation. These observations provide new insights regarding the transitions required for intercalation of a phosphodiester-ribose backbone and suggest a possible contribution of the backbone to the origin of the nearest-neighbor exclusion principle. Thermodynamic studies presented for intercalation of both structural RNA isomers also reveal a surprising sensitivity of intercalator binding enthalpy and entropy to the details of RNA backbone structure.

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Solution structure of a modified 2',5'-linked RNA hairpin involved in an equilibrium with duplex

Cited by 10 publications

References 40 publications

The solution structure of double helical arabino nucleic acids (ANA and 2′F-ANA): effect of arabinoses in duplex-hairpin interconversion

The solution structure of double helical arabino nucleic acids (ANA and 2′F-ANA): effect of arabinoses in duplex-hairpin interconversion

Solution-state structure of a fully alternately 2′-F/2′-OMe modified 42-nt dimeric siRNA construct

Solution Structure and Thermodynamics of 2′,5′ RNA Intercalation

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