Effects of N2,N2-dimethylguanosine on RNA structure and stability: Crystal structure of an RNA duplex with tandem m22G:A pairs

Pallan, Pradeep S.; Kreutz, Christoph; Bosio, Silvia; Micura, Ronald; Egli, Martin

doi:10.1261/rna.1078508

Cited by 55 publications

(47 citation statements)

References 45 publications

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“…The model shown in Fig. 15 of m 2 2 G26:A44 is energetically feasible as found in crystal structure of RNA duplex dimmer [56]. The hydrophobic effect of N 2 -dimethyl group of m 2 2 G26 would not allow to interact with C44.…”

Section: Automated Full Geometry Optimizationmentioning

confidence: 86%

Conformational Preferences of Modified Nucleoside N2-methylguanosine (m2G) and Its Derivative N2, N2-dimethylguanosine (m 2 2 G) Occur at 26th Position (Hinge Region) in tRNA

Bavi

Kamble

Kumbhar

et al. 2011

Cell Biochem Biophys

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Conformational preferences of the modified nucleosides N(2)-methylguanosine (m(2)G) and N(2), N(2)-dimethylguanosine (m(2)(2)G) have been studied theoretically by using quantum chemical perturbative configuration interaction with localized orbitals (PCILO) method. Automated complete geometry optimization using semiempirical quantum chemical RM1, along with ab initio molecular orbital Hartree-Fock (HF-SCF), and density functional theory (DFT) calculations has also been made to compare the salient features. Single-point energy calculation studies have been made on various models of m(2)G26:C/A/U44 and m(2)(2)G26:C/A/U44. The glycosyl torsion angle prefers "syn" (χ = 286°) conformation for m(2)G and m(2)(2)G molecules. These conformations are stabilized by N(3)-HC2' and N(3)-HC3' by replacing weak interaction between O5'-HC(8). The N(2)-methyl substituent of (m(2)G26) prefers "proximal" or s-trans conformation. It may also prefer "distal" or s-cis conformation that allows base pairing with A/U44 instead of C at the hinge region. Thus, N(2)-methyl group of m(2)G may have energetically two stable s-trans m(2)G:C/A/U or s-cis m(2)G:A/U rotamers. This could be because of free rotations around C-N bond. Similarly, N(2), N(2)-dimethyl substituent of (m(2)(2)G) prefers "distal" conformation that may allow base pairing with A/U instead of C at 44th position. Such orientations of m(2)G and m(2)(2)G could play an important role in base-stacking interactions at the hinge region of tRNA during protein biosynthesis process.

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Section: Automated Full Geometry Optimizationmentioning

confidence: 86%

Conformational Preferences of Modified Nucleoside N2-methylguanosine (m2G) and Its Derivative N2, N2-dimethylguanosine (m 2 2 G) Occur at 26th Position (Hinge Region) in tRNA

Bavi

Kamble

Kumbhar

et al. 2011

Cell Biochem Biophys

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“…m 2 2 G26: Without exception, all 25 sites belong to the high group. This modification is known to provide rigidity of the coaxially stacked D and anticodon stems (Steinberg and Cedergren 1995) and to prevent misfolding of at least one tRNA (Edqvist et al 1995;Pallan et al 2008). Full modification at these sites would ensure that these tRNAs all have proper conformations and rigidity for translation.…”

Section: Assessment Of Quantification Of Methylation Fractionsmentioning

confidence: 99%

tRNA base methylation identification and quantification via high-throughput sequencing

Clark¹,

Evans²,

Dominissini

et al. 2016

RNA

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Eukaryotic transfer RNAs contain on average 14 modifications. Investigations of their biological functions require the determination of the modification sites and the dynamic variations of the modification fraction. Base methylation represents a major class of tRNA modification. Although many approaches have been used to identify tRNA base methylations, including sequencing, they are generally qualitative and do not report the information on the modification fraction. Dynamic mRNA modifications have been shown to play important biological roles; yet, the extent of tRNA modification fractions has not been reported systemically. Here we take advantage of a recently developed high-throughput sequencing method (DM-tRNA-seq) to identify and quantify tRNA base methylations located at the Watson-Crick face in HEK293T cells at single base resolution. We apply information derived from both base mutations and positional stops from sequencing using a combination of demethylase treatment and cDNA synthesis by a thermophilic reverse transcriptase to compile a quantitative "Modification Index" (MI) for six base methylations in human tRNA and rRNA. MI combines the metrics for mutational and stop components from alignment of sequencing data without demethylase treatment, and the modifications are validated in the sequencing data upon demethylase treatment. We identify many new methylation sites in both human nuclear and mitochondrial-encoded tRNAs not present in the RNA modification databases. The potentially quantitative nature of the MI values obtained from sequencing is validated by primer extension of several tRNAs. Our approach should be widely applicable to identify tRNA methylation sites, analyze comparative fractional modifications, and evaluate the modification dynamics between different samples.

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“…7,[12][13][14] We therefore decided to explore labeling of RNA at the guanosine sugar edge in an siRNA model system. Research associated with RNA interference, 15 a process that moderates gene expression in cells, is often accompanied by fluorescent labeling of the siRNAs.…”

mentioning

confidence: 99%

A modified guanosine phosphoramidite for click functionalization of RNA on the sugar edge

et al. 2012

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Effects of N²,N²-dimethylguanosine on RNA structure and stability: Crystal structure of an RNA duplex with tandem m²₂G:A pairs

Cited by 55 publications

References 45 publications

Conformational Preferences of Modified Nucleoside N2-methylguanosine (m2G) and Its Derivative N2, N2-dimethylguanosine (m 2 2 G) Occur at 26th Position (Hinge Region) in tRNA

Conformational Preferences of Modified Nucleoside N2-methylguanosine (m2G) and Its Derivative N2, N2-dimethylguanosine (m 2 2 G) Occur at 26th Position (Hinge Region) in tRNA

tRNA base methylation identification and quantification via high-throughput sequencing

A modified guanosine phosphoramidite for click functionalization of RNA on the sugar edge

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