Influence of C-5 halogenation of uridines on hairpin versus duplex RNA folding

Ennifar, Eric; Bernacchi, Serena; Wolff, Philippe; Dumas, Philippe

doi:10.1261/rna.408507

Cited by 23 publications

(12 citation statements)

References 34 publications

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“…We came up with an atlas of 27 unique modified base pairs containing naturally occurring modifications, differing by the nucleobase combination and/or base pairing geometry. Nine additional pairs involving non-natural modified bases, specifically halogenated pyrimidines used to solve the crystallographic phase problem, were also retained in our analysis, as the question has been raised whether this kind of modification can interfere with the functional RNA folding ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies

et al. 2015

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Posttranscriptional modifications greatly enhance the chemical information of RNA molecules, contributing to explain the diversity of their structures and functions. A significant fraction of RNA experimental structures available to date present modified nucleobases, with half of them being involved in H-bonding interactions with other bases, i.e. ‘modified base pairs’. Herein we present a systematic investigation of modified base pairs, in the context of experimental RNA structures. To this end, we first compiled an atlas of experimentally observed modified base pairs, for which we recorded occurrences and structural context. Then, for each base pair, we selected a representative for subsequent quantum mechanics calculations, to find out its optimal geometry and interaction energy. Our structural analyses show that most of the modified base pairs are non Watson–Crick like and are involved in RNA tertiary structure motifs. In addition, quantum mechanics calculations quantify and provide a rationale for the impact of the different modifications on the geometry and stability of the base pairs they participate in.

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Section: Introductionmentioning

confidence: 99%

An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies

et al. 2015

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“…As shown previously, this protocol essentially leads to the formation of DIS loop-loop dimers and prevents the formation of extended duplex dimers. 83,84 A similar protocol was performed for folding of TAR and SRL hairpins. DIS-A272U/ΔG273 was diluted to 60 μM in water, heated at 90°C for 5 min and then cooled at room temperature.…”

Section: Fundingmentioning

confidence: 99%

Sequence and structure requirements for specific recognition of HIV-1 TAR and DIS RNA by the HIV-1 Vif protein

et al. 2012

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The HIV-1 Vif protein plays an essential role in the regulation of the infectivity of HIV-1 virion and in vivo pathogenesis. Vif neutralizes the human DNA-editing enzyme APOBEC3 protein, an antiretroviral cellular factor from the innate immune system, allowing the virus to escape the host defence system. It was shown that Vif is packaged into viral particles through specific interactions with the viral genomic RNA. Conserved and structured sequences from the 5'-noncoding region, such as the Tat-responsive element (TAR) or the genomic RNA dimerization initiation site (DIS), are primary binding sites for Vif. In the present study we used isothermal titration calorimetry to investigate sequence and structure determinants important for Vif binding to short viral RNA corresponding to TAR and DIS stem-loops. We showed that Vif specifically binds TAR and DIS in the low nanomolar range. In addition, Vif primarily binds the TAR UCU bulge, but not the apical loop. Determinants for Vif binding to the DIS loop-loop complex are likely more complex and involve the self-complementary loop together with the upper part of the stem. These results suggest that Tat-TAR inhibitors or DIS small molecule binders might be also effective to disturb Vif-TAR and Vif-DIS binding in order to reduce Vif packaging into virions.

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“…Data were collected at 90 K on a Pilatus 6M detector (Dectris AG) on five U2656-SeCH 3 SRL crystals, two U267-SeCH 3 DIS duplex/ Ribostamycin crystals (Freisz et al 2008), four U267-Bromo DIS kissing-complex/Lividomycin crystals (Ennifar et al 2006), and three U267-Iodo DIS kissing-complex/Lividomycin crystals (Ennifar et al 2007a). Data for seleno and iodo derivatives were collected at 12.6647 keV and at 13.4895 keV for bromo derivatives.…”

Section: Site-specific Radiation Damage Analysismentioning

confidence: 99%

A fast selenium derivatization strategy for crystallization and phasing of RNA structures

Oliéric¹,

Rieder²,

Lang³

et al. 2009

RNA

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Site-specific 29-methylseleno RNA labeling is a promising tool for tackling the phase problem in RNA crystallography. We have developed an efficient strategy for crystallization and structure determination of RNA and RNA/protein complexes based on preliminary crystallization screening of 29-OCH 3 -modified RNA sequences, prior to the replacement of 29-OCH 3 groups with their 29-SeCH 3 counterparts. The method exploits the similar crystallization properties of 29-OCH 3 -and 29-SeCH 3 -modified RNAs and has been successfully validated for two test cases. In addition, our data show that 29-SeCH 3 -modified RNA have an increased resistance to X-ray radiolysis in comparison with commonly used 5-halogen-modified RNA, which permits collection of experimental electron density maps of remarkable quality.

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Influence of C-5 halogenation of uridines on hairpin versus duplex RNA folding

Cited by 23 publications

References 34 publications

An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies

An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies

Sequence and structure requirements for specific recognition of HIV-1 TAR and DIS RNA by the HIV-1 Vif protein

A fast selenium derivatization strategy for crystallization and phasing of RNA structures

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