<i>S</i>‐Geranylated 2‐Thiouridines of Bacterial tRNAs: Chemical Synthesis and Physicochemical Properties

Leszczyńska, Grażyna; Sadowska, Klaudia; Bartos, Paulina; Nawrot, Barbara; Sochacka, Elżbieta

doi:10.1002/ejoc.201600519

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…The reported unexpected higher mobility (shorter retention time in RP-HPLC) of the geranylated product compared to its native precursor (T instead of geS2T) was explained by the Authors as ‘a special structural alignment in the oligonucleotide’ (15). Our observations are in agreement with recently obtained log P data determined at the level of R5geS2U nucleosides (R = H, mnm or cmnm), which indicate a higher lipophilicity of these compounds compared to their parent R5S2Us (16). In the present studies, we measured the partition coefficients of the U, S and geS oligonucleotides in a water/1-octanol biphasic system.…”

Section: Discussionsupporting

confidence: 92%

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S-Geranyl-2-thiouridine wobble nucleosides of bacterial tRNAs; chemical and enzymatic synthesis ofS-geranylated-RNAs and their physicochemical characterization

et al. 2016

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Recently, highly lipophilic S-geranylated derivatives of 5-methylaminomethyl-2-thiouridine (mnm5geS2U) and 5-carboxymethylaminomethyl-2-thiouridine (cmnm5geS2U) were found at the first (wobble) anticodon position in bacterial tRNAs specific for Lys, Glu and Gln. The function and cellular biogenesis of these unique tRNAs remain poorly understood. Here, we present one direct and two post-synthetic chemical routes for preparing model geS2U-RNAs. Our experimental data demonstrate that geS2U-RNAs are more lipophilic than their parent S2U-RNAs as well as non-modified U-RNAs. Thermodynamic studies revealed that the S-geranyl-2-thiouridine-containing RNA has higher affinity toward complementary RNA strand with G opposite the modified unit than with A. Recombinant tRNA selenouridine synthase (SelU) exhibits sulfur-specific geranylation activity toward model S2U-RNA, which is composed of the anticodon-stem-loop (ASL) from the human tRNALys3 sequence. In addition, the presence of magnesium ions is required to achieve appreciable geranylation efficiencies.

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Section: Discussionsupporting

confidence: 92%

“…Escherichia coli, Enterobacter aerogenes, Pseudomonas aeruginosa and Salmonella Typhimurium ), detailed data on the properties and cellular functions of these tRNAs have not been reported, with the exception of data on the hydrophobicity and structural characteristics of mnm5geS2U and cmnm5geS2U at the nucleoside level (16). …”

Section: Introductionmentioning

confidence: 99%

S-Geranyl-2-thiouridine wobble nucleosides of bacterial tRNAs; chemical and enzymatic synthesis ofS-geranylated-RNAs and their physicochemical characterization

et al. 2016

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“…We previously reported that bands around 240 nm may be attributed to a conjugated C2=N3-C4=O4 π-bond system present in 4-pyrimidinone-like scaffolds, e.g., in S-geranylated-2-thiouridine (λ max ca. 240 nm) [76], 4-pyrimidinone riboside (λ max ca. 247 nm for mnm5H2U) [77], and 5-methyl-4-pyrimidinone 2 -deoxyriboside (λ max ca.…”

Section: Discussionmentioning

confidence: 99%

C5-Substituted 2-Selenouridines Ensure Efficient Base Pairing with Guanosine; Consequences for Reading the NNG-3′ Synonymous mRNA Codons

Leszczyńska

Cypryk

Gostyński

et al. 2020

IJMS

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5-Substituted 2-selenouridines (R5Se2U) are post-transcriptional modifications present in the first anticodon position of transfer RNA. Their functional role in the regulation of gene expression is elusive. Here, we present efficient syntheses of 5-methylaminomethyl-2-selenouridine (1, mnm5Se2U), 5-carboxymethylaminomethyl-2-selenouridine (2, cmnm5Se2U), and Se2U (3) alongside the crystal structure of the latter nucleoside. By using pH-dependent potentiometric titration, pKa values for the N3H groups of 1-3 were assessed to be significantly lower compared to their 2-thio-and 2-oxo-congeners. At physiological conditions (pH 7.4), Se2-uridines 1 and 2 preferentially adopted the zwitterionic form (ZI, ca. 90%), with the positive charge located at the amino alkyl side chain and the negative charge at the Se2-N3-O4 edge. As shown by density functional theory (DFT) calculations, this ZI form efficiently bound to guanine, forming the so-called "new wobble base pair", which was accepted by the ribosome architecture. These data suggest that the tRNA anticodons with wobble R5Se2Us may preferentially read the 5 -NNG-3 synonymous codons, unlike their 2-thio-and 2-oxo-precursors, which preferentially read the 5 -NNA-3 codons. Thus, the interplay between the levels of U-, S2U-and Se2U-tRNA may have a dominant role in the epitranscriptomic regulation of gene expression via reading of the synonymous 3 -A-and 3 -G-ending codons.

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“…The excess selenium was filtered off and vacuum distillation (b.p. 51-52°C/0.1 mmHg) of the filtrate furnished O,O,O-tris(trimethylsilyl) phosphoroselenoate (1.67 g, 0.0044 mol), 63% yield; spectral data: 31…”

Section: Synthesis Of Selenophosphate Sepo 3 3àmentioning

confidence: 99%

“…2A) shows that the retention times (R T ) for U-RNA, S2U-RNA, and Se2U-RNA are very similar (ca. 28 min) while the geS2U-RNA elutes at significantly higher concentration of the organic phase (R T > 41 min) because of the presence of the hydrophobic geranyl group [21,31]. The MALDI-TOF MS analysis of the 1 : 1 mixture of S2U-RNA and Se2U-RNA shows the corresponding signals of virtually the same intensity (Fig.…”

Section: Synthesis and Characteristics Of Rna Modelsmentioning

confidence: 99%

Escherichia coli tRNA 2‐selenouridine synthase (SelU) converts S2U‐RNA to Se2U‐RNA via S‐geranylated‐intermediate

et al. 2018

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To date the only tRNAs containing nucleosides modified with a selenium (5-carboxymethylaminomethyl-2-selenouridine and 5-methylaminomethyl-2-selenouridine) have been found in bacteria. By using tRNA anticodon-stem-loop fragments containing S2U, Se2U, or geS2U, we found that in vitro tRNA 2-selenouridine synthase (SelU) converts S2U-RNA to Se2U-RNA in a two-step process involving S2U-RNA geranylation (with ppGe) and subsequent selenation of the resulting geS2U-RNA (with SePO ). No 'direct' S2U-RNA→Se2U-RNA replacement is observed in the presence of SelU/SePO only (without ppGe). These results suggest that the in vivo S2U→Se2U and S2U→geS2U transformations in tRNA, so far claimed to be the elementary reactions occurring independently in the same domain of the SelU enzyme, should be considered a combination of two consecutive events - geranylation (S2U→geS2U) and selenation (geS2U→Se2U).

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S‐Geranylated 2‐Thiouridines of Bacterial tRNAs: Chemical Synthesis and Physicochemical Properties

Cited by 8 publications

References 21 publications

S-Geranyl-2-thiouridine wobble nucleosides of bacterial tRNAs; chemical and enzymatic synthesis ofS-geranylated-RNAs and their physicochemical characterization

S-Geranyl-2-thiouridine wobble nucleosides of bacterial tRNAs; chemical and enzymatic synthesis ofS-geranylated-RNAs and their physicochemical characterization

C5-Substituted 2-Selenouridines Ensure Efficient Base Pairing with Guanosine; Consequences for Reading the NNG-3′ Synonymous mRNA Codons

Escherichia coli tRNA 2‐selenouridine synthase (SelU) converts S2U‐RNA to Se2U‐RNA via S‐geranylated‐intermediate

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