The tetraribonucleotiderCpGpCpG forms a left-handed Z-RNA double-helix

Davis, Peter W.; Hall, Kathleen B.; Cruz, Phillip; Tinoco, Ignacio; Neilson, Thomas

doi:10.1093/nar/14.3.1279

Cited by 40 publications

(22 citation statements)

References 19 publications

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“…Remarkably, the same CD spectrum is provided by the Z-RNA duplex of r(CGCGCG) (Fig. 5, inset B ;Hall et al, 1984;Davis et al, 1986). The CD spectrum contains the negative band close to 200 nm characteristic for left-handed DNA duplexes (Riazance et al, 1987).…”

Section: Wavelength [Nm]supporting

confidence: 53%

Comparison of the solution and crystal conformations of (G + C)-rich fragments of DNA

Vorlı́čková

Subirana

Chládková

et al. 1996

Biophysical Journal

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DNA fragments crystallize in an unpredictable manner, and relationships between their crystal and solution conformations still are not known. We have studied, using circular dichroism spectroscopy, solution conformations of (G + C)-rich DNA fragments, the crystal structures of which were solved in the laboratory of one of the present authors. In aqueous trifluorethanol (TFE) solutions, all of the examined oligonucleotides adopted the same type of double helix as in the crystal. Specifically, the dodecamer d(CCCCCGCGGGGG) crystalized as A-DNA and isomerized into A-DNA at high TFE concentrations. On the other hand, the hexamer d(CCGCGG) crystallized in Z-form containing tilted base pairs, and high TFE concentrations cooperatively transformed it into the same Z-form as adopted by the RNA hexamer r(CGCGCG), although d(CCGCGG) could isomerize into Z-DNA in the NaCl + NiCl2) aqueous solution. The fragments crystallizing as B-DNA remained B-DNA, regardless of the solution conditions, unless they denatured or aggregated. Effects on the oligonucleotide conformation of 2-methyl-2,4-pentanediol and other crystallization agents were also studied. 2-Methyl-2,4-pentanediol induced the same conformational transitions as TFE but, in addition, caused an oligonucleotide condensation that was also promoted by the other crystallization agents. The present results indicate that the crystal double helices of DNA are stable in aqueous TFE rather than aqueous solution.

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Section: Wavelength [Nm]supporting

confidence: 53%

Comparison of the solution and crystal conformations of (G + C)-rich fragments of DNA

Vorlı́čková

Subirana

Chládková

et al. 1996

Biophysical Journal

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“…The crystal structures of nucleosides and nucleotides 23 and solution phase NMR studies [24][25][26][27][28][29] suggest that the conformation of the sugar ring can be adequately described by two conformations such as the C3′-endo-C2′-exo (North sugar) and C2′-endo- Values are for radicals formed via photoexcitation at 143 K in the frozen aqueous (7.5 M LiCl D2O) glassy solution with native pH (ca. 5).…”

Section: Detection Of Sugar Radical Components In Glassy Samples Of Gmentioning

confidence: 99%

Formation of Sugar Radicals in RNA Model Systems and Oligomers via Excitation of Guanine Cation Radical

et al. 2008

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In previous work, we have shown that photoexcitation of guanine cation radical (G*+) in frozen aqueous solutions of DNA and its model compounds at 143 K results in the formation of neutral sugar radicals with substantial yield. In this report, we present electron spin resonance (ESR) and theoretical (DFT) evidence regarding the formation of sugar radicals after photoexcitation of guanine cation radical (G*+) in frozen aqueous solutions of one-electron-oxidized RNA model compounds (nucleosides, nucleotides and oligomers) at 143 K. Specific sugar radicals C5'*, C3'* and C1'* were identified employing derivatives of Guo deuterated at specific sites in the sugar moiety, namely, C1'-, C2'-, C3'- and C5'-. These results suggest C2'* is not formed upon photoexcitation of G*+ in one-electron-oxidized Guo and deuterated Guo derivatives. Phosphate substitution at C5'- (i.e., in 5-GMP) hinders formation of C5'* via photoexcitation at 143 K but not at 77 K. For the RNA-oligomers studied, we observe on photoexcitation of oligomer-G*+ the formation of mainly C1'* and an unidentified radical with a ca. 28 G doublet. The hyperfine coupling constants of each of the possible sugar radicals were calculated employing the DFT B3LYP/6-31G* approach for comparison to experiment. This work shows that formation of specific neutral sugar radicals occurs via photoexcitation of guanine cation radical (G*+) in RNA systems but not by photoexcitation of its N1 deprotonated species (G(-H)*). Thus, our mechanism regarding neutral sugar formation via photoexcitation of base cation radicals in DNA appears to be valid for RNA systems as well.

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“…To characterise whether the sequences surrounding Za-dependent editing sites have a propensity to form Z-RNA, we analysed sequences 500 nt up-and down-stream of editing sites. We tested GC content, given that GC-repeats have a higher tendency to adopt the Z-conformation (Davis et al, 1986). There was no enrichment of GC dinucleotides, or other motifs, around differentially edited sites compared to all detected sites (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike canonical B-DNA, a right-handed double helix, Z-DNA is a left-handed double helix with a zig-zag-shaped phosphodiester back bone (Wang et al, 1979). dsRNA can also adopt the Z-conformation (Davis et al, 1986;Hall et al, 1984). Biological functions of Z nucleic acids, in particular those of Z-RNA, are incompletely understood (Herbert, 2019).…”

Section: Introductionmentioning

confidence: 99%

Recognition of Z-RNA by ADAR1 limits interferon responses

Tang

Rigby

Young

et al. 2020

Preprint

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Nucleic acids are powerful triggers of innate immunity and can adopt the unusual Z-conformation. The p150 isoform of adenosine deaminase acting on RNA 1 (ADAR1) prevents aberrant interferon (IFN) induction and contains a Z-nucleic acid binding (Zα) domain. We report that knock-in mice bearing two point mutations in the Zα domain of ADAR1, which abolish binding to Z-form nucleic acids, spontaneously induced type I IFNs and IFN-stimulated genes (ISGs) in multiple organs. This included the lung where both stromal and haematopoietic cells displayed ISG induction in Adar1mZα/mZα mice. Concomitantly, Adar1mZα/mZα mice showed improved control of influenza A virus. The spontaneous IFN response in Adar1mZα/mZα mice required MAVS, implicating cytosolic RNA sensing. Finally, analysis of A-to-I changes revealed a specific requirement of ADAR1’s Zα domain in editing of a subset of RNAs. In summary, our results reveal that endogenous RNAs in Z-conformation have immunostimulatory potential that is curtailed by ADAR1.

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The tetraribonucleotide_rC_pG_pC_pG forms a left-handed Z-RNA double-helix

Cited by 40 publications

References 19 publications

Comparison of the solution and crystal conformations of (G + C)-rich fragments of DNA

Comparison of the solution and crystal conformations of (G + C)-rich fragments of DNA

Formation of Sugar Radicals in RNA Model Systems and Oligomers via Excitation of Guanine Cation Radical

Recognition of Z-RNA by ADAR1 limits interferon responses

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