tRNA Phe Research Articles

The crystal structure of unmodified tRNA Phe from Escherichia coli

Post-transcriptional nucleoside modifications fine-tune the biophysical and biochemical properties of transfer RNA (tRNA) so that it is optimized for participation in cellular processes. Here we report the crystal structure of unmodified tRNAPhe from Escherichia coli at a resolution of 3 Å. We show that in the absence of modifications the overall fold of the tRNA is essentially the same as that of mature tRNA. However, there are a number of significant structural differences, such as rearrangements in a triplet base pair and a widened angle between the acceptor and anticodon stems. Contrary to previous observations, the anticodon adopts the same conformation as seen in mature tRNA.

Mitochondrial genome of Thais clavigera (Mollusca: Gastropoda): Affirmation of the conserved, ancestral gene pattern within the mollusks

Class Gastropoda includes a large number of described species, many with extensively rearranged mitochondrial genomes. We sequenced the mitogenome of the rock shell, Thais clavigera (Gastropoda: Muricidae), an intertidal snail, using long PCR with primers designed on the basis of expressed sequence tags. The mitogenome of T. clavigera consists of 2 rRNAs, 22 tRNAs, and 13 protein-coding genes, but no control region. Structural comparisons revealed that the order Sorbeoconcha, including T. clavigera, have nearly identical mitochondrial gene patterns. However, they have an inversion between a tRNA(Phe)-tRNA(Glu) cluster that comprises 21 genes, but most of the remaining structure is similar to the putative mollusk ground pattern. These findings will provide a better insight into mitochondrial gene rearrangement over the course of gastropod evolution.

The NEXT-A (N-Terminal EXtension with Transferase and ARS) reaction

L/F-transferase is known to catalyze transfer of hydrophobic amino acids from aminoacyl tRNA to the N-terminus of a protein possessing lysine or arginine as the N-terminus. Combining L/F-transferase with E. coli phenylalanyl-tRNA synthetase (ARS), we achieved non-ribosomal N-terminal-specific introduction of various kinds of nonnatural amino acids to a protein. A nonnatural amino acid is once charged onto an E. coli tRNA(Phe) by a mutant ARS in situ, and successively transferred from the tRNA to a target protein, namely the NEXT-A reaction. Besides alphaA294G mutation on the ARS, alphaT251A, betaG318W, or betaA356W double-mutation were effective to increase the introduction efficiency through the NEXT-A reaction. Protein specific fluorescence labelling via the NEXT-A reaction followed by Huisgen cycloaddition was also demonstrated.

Ribosomal frameshifting in response to hypomodified tRNAs in Xenopus oocytes

The question of whether hypomodified tRNAs enhanced mammalian retroviral ribosomal frameshifting (RF) was resolved several years ago when Phe tRNA lacking the highly modified wyebutoxine (Y) base at position 37 enhanced RF in retroviruses using UUU at the frameshift site (Carlson et al. Virology 255: 2, 1999). However, the level of RF in this earlier study and subsequent studies (Carlson et al. Virology 279: 130, 2001; Waas et al. JBC 282: 26026, 2007) far exceeded that naturally found with mammalian retroviruses which raised concerns whether Phe tRNA ‐Y only enhanced RF or was actually required for the event to occur. In the present study, we examined Xenopus oocytes as an "in vivo" protein synthesis system to assess whether the important issue of only an enhancement vs. an essential requirement could be resolved. Microinjection of oocytes with a construct encoding UUU at the frameshift site demonstrated that the level of RF was lower than that found naturally in retroviral RF, while co‐injection with Phe tRNA ‐Y enhanced RF and co‐injection with Phe tRNA +Y inhibited RF. Thus, Phe tRNA ‐Y does not only enhance RF, but is an essential requirement. This finding provides a novel avenue of inhibiting retroviral expression by reducing the level of intracellular hypomodified tRNA. This research was supported by the Intramural Research Program of the NIH, NCI, CCR.

Interaction of human phenylalanyl-tRNA synthetase with specific tRNA according to thiophosphate footprinting

The interaction of human cytoplasmic phenylalanyl-tRNA synthetase (an enzyme with yet unknown 3D-structure) with homologous tRNA(Phe) under functional conditions was studied by footprinting based on iodine cleavage of thiophosphate-substituted tRNA transcripts. Most tRNA(Phe) nucleotides recognized by the enzyme in the anticodon (G34), anticodon stem (G30-C40, A31-U39), and D-loop (G20) have effectively or moderately protected phosphates. Other important specificity elements (A35 and A36) were found to form weak nonspecific contacts. The D-stem, T-arm, and acceptor stem are also among continuous contacts of the tRNA(Phe) backbone with the enzyme, thus suggesting the presence of additional recognition elements in these regions. The data indicate that mechanisms of interaction between phenylalanyl-tRNA synthetases and specific tRNAs are different in prokaryotes and eukaryotes.

Mutation in MTO1 involved in tRNA modification impairs mitochondrial RNA metabolism in the yeast Saccharomyces cerevisiae

The yeast MTO1 gene encodes an evolutionarily conserved protein for the biosynthesis of the 5-carboxymethylaminomethyl group of cmnm 5s 2U in the wobble position of mitochondrial tRNA. However, mto1 null mutant expressed the respiratory deficient phenotype only when coupled with the C1409G mutation of mitochondrial 15S rRNA. To further understand the role of MTO1 in mitochondrial RNA metabolism, the yeast mto1 null mutants carrying either wild-type (P S) or 15S rRNA C1409G allele (P R) have been characterized by examining the steady-state levels, aminoacylation capacity of mitochondrial tRNA, mitochondrial gene expression and petite formation. The steady-state levels of tRNA Lys, tRNA Glu, tRNA Gln, tRNA Leu, tRNA Gly, tRNA Arg and tRNA Phe were decreased significantly while those of tRNA Met and tRNA His were not affected in the mto1 strains carrying the P S allele. Strikingly, the combination of the mto1 and C1409G mutations gave rise to the synthetic phenotype for some of the tRNAs, especially in tRNA Lys, tRNA Met and tRNA Phe. Furthermore, the mto1 strains exhibited a marked reduction in the aminoacylation levels of mitochondrial tRNA Lys, tRNA Leu, tRNA Arg but almost no effect in those of tRNA His. In addition, the steady-state levels of mitochondrial COX1, COX2, COX3, ATP6 and ATP9 mRNA were markedly decreased in mto1 strains. These data strongly indicate that unmodified tRNA caused by the deletion of MTO1 gene caused the instability of mitochondrial tRNAs and mRNAs and an impairment of aminoacylation of mitochondrial tRNAs. Consequently, the deletion of MTO1 gene acts in synergy with the 15S rRNA C1409G mutation, leading to the loss of COX1 synthesis and subsequent respiratory deficient phenotype.

Understanding the Sequence Specificity of tRNA Binding to Elongation Factor Tu using tRNA Mutagenesis

Measuring the binding affinities of 42 single-base-pair mutants in the acceptor and TΨC stems of Saccharomyces cerevisiae tRNA Phe to Thermus thermophilus elongation factor Tu (EF-Tu) revealed that much of the specificity for tRNA occurs at the 49–65, 50–64, and 51–63 base pairs. Introducing the same mutations at the three positions into Escherichia coli tRNA CAG Leu resulted in similar changes in binding affinity. Swapping the three pairs from several E. coli tRNAs into yeast tRNA Phe resulted in chimeras with EF-Tu binding affinities similar to those for the donor tRNA. Finally, analysis of double- and triple-base-pair mutants of tRNA Phe showed that the thermodynamic contributions at the three sites are additive, permitting reasonably accurate prediction of the EF-Tu binding affinity for all E. coli tRNAs. Thus, it appears that the thermodynamic contributions of three base pairs in the TΨC stem primarily account for tRNA binding specificity to EF-Tu.

Ribosomal frameshifting in response to hypomodified tRNAs in Xenopus oocytes

We used Xenopus oocytes as an intracellular system to study ribosomal frameshifting. Microinjection of oocytes with a construct encoding the naturally occurring UUU or AAC codon at the frameshift site demonstrated that the level of frameshifting was similar or lower than found normally in retroviral frameshifting in mammalian cells, suggesting that oocytes are a reliable system to study this event. Phenylalanine (Phe) or asparagine (Asn) tRNAs with and without the highly modified wyebutoxine (Y) or queuosine (Q) base, respectively, were microinjected to assess their ability to promote frameshifting. tRNA Phe +Y inhibited the level of frameshifting, while tRNA Phe −Y promoted frameshifting providing evidence that the hypomodified form does not act only to enhance frameshifting, but is an essential requirement. Both tRNA Asn +Q and tRNA Asn −Q were used indiscriminately in frameshifting, whether the frameshift site contained the wild-type AAC, or the mutant AAU codon, suggesting that Q base modification status does not influence this process.

Binding of DNA-binding alkaloids berberine and palmatine to tRNA and comparison to ethidium: Spectroscopic and molecular modeling studies

The interaction of two natural protoberberine plant alkaloids berberine and palmatine with tRNA phe was studied using various biophysical techniques and molecular modeling and the data were compared with the binding of the classical DNA intercalator, ethidium. Circular dichroic studies revealed that the tRNA conformation was moderately perturbed on binding of the alkaloids. The cooperative binding of both the alkaloids and ethidium to tRNA was revealed from absorbance and fluorescence studies. Fluorescence quenching studies advanced a conclusion that while berberine and palmatine are partially intercalated, ethidium is fully intercalated on the tRNA molecule. The binding of the alkaloids as well as ethidium stabilized the tRNA melting, and the binding constant evaluated from the averaged optical melting temperature data was in agreement with fluorescence spectral-binding data. Differential scanning calorimetry revealed that the tRNA melting showed three close transitions that were affected on binding of these small molecules. Molecular docking calculations performed showed the preferred regions of binding of these small molecules on the tRNA. Taken together, the results suggest that the binding of the alkaloids berberine and palmatine on the tRNA structure appears to be mostly by partial intercalation while ethidium intercalates fully on the tRNA. These results further advance our knowledge on the molecular aspects on the interaction of these alkaloids to tRNA.

DNA and Cell Biology 2008 New Year's Resolutions

DNA and Cell BiologyVol. 27, No. 1 EditorialDNA and Cell Biology 2008 New Year's ResolutionsPublished Online:21 Jan 2008https://doi.org/10.1089/dna.2008.1500AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "DNA and Cell Biology 2008 New Year's Resolutions." , 27(1), p. 1FiguresReferencesRelatedDetailsCited bySpectroscopic and molecular docking investigation of polynucleotides and DNA binding affinity to Nile blue dye7 February 2019 | Biotechnic & Histochemistry, Vol. 94, No. 4Spectroscopic Study of the Binding of Netropsin and Hoechst 33258 to Nucleic Acids7 May 2018 | Journal of Applied Spectroscopy, Vol. 85, No. 2Thermodynamic analysis of the complexation of quinacrine with tRNA PheThe Journal of Chemical Thermodynamics, Vol. 120Experimental and computational studies on the effects of valganciclovir as an antiviral drug on calf thymus DNA19 October 2016 | Nucleosides, Nucleotides and Nucleic Acids, Vol. 36, No. 1Exploring the interaction of phenothiazinium dyes methylene blue, new methylene blue, azure A and azure B with tRNA Phe : spectroscopic, thermodynamic, voltammetric and molecular modeling approach1 January 2017 | Physical Chemistry Chemical Physics, Vol. 19, No. 9DNA-binding, DNA cleavage and cytotoxicity studies of two anthraquinone derivativesSpectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Vol. 87DNA Binding and Gel Electrophoresis Studies of a New Silver(I) Complex Containing 2,9-Dimethyl-1,10-Phenanthroline Ligands Nahid Shahabadi, Soheila Kashanian, and Zeinab Ahmadipour1 March 2011 | DNA and Cell Biology, Vol. 30, No. 3Histone H1 Structural Changes and its Interaction with DNA in the Presence of High Glucose Concentration In Vivo and In VitroJournal of Biomolecular Structure and Dynamics, Vol. 28, No. 4The Promotive Effects of Antioxidative Apigenin on the Bioavailability of Paclitaxel for Oral Delivery in RatsBiomolecules and Therapeutics, Vol. 18, No. 4Methyl thiophanate as a DNA minor groove binder produces MT–Cu(II)–DNA ternary complex preferably with AT rich region for initiation of DNA damageInternational Journal of Biological Macromolecules, Vol. 47, No. 1In Vitro Study of DNA Interaction with a Water-Soluble Dinitrogen Schiff Base Nahid Shahabadi, Soheila Kashanian, and Farivash Darabi26 October 2009 | DNA and Cell Biology, Vol. 28, No. 11In Vitro Study of Calf Thymus DNA Interaction with Butylated Hydroxyanisole Soheila Kashanian and Jafar Ezzati Nazhad Dolatabadi22 September 2009 | DNA and Cell Biology, Vol. 28, No. 10A Comparative Study on the Interaction of Cis- and Trans-Platin with DNA and RNA Shohreh Nafisi and Zeinab Norouzi26 August 2009 | DNA and Cell Biology, Vol. 28, No. 9Enhancement of Cisplatin [ cis -Diammine Dichloroplatinum (II)] Cytotoxicity by O6 -Benzylguanine Involves Endoplasmic Reticulum Stress29 July 2008 | Journal of Pharmacology and Experimental Therapeutics, Vol. 327, No. 2 Volume 27Issue 1Jan 2008 InformationCopyright 2008, Mary Ann Liebert, Inc.To cite this article:DNA and Cell Biology 2008 New Year's Resolutions.DNA and Cell Biology.Jan 2008.1-1.http://doi.org/10.1089/dna.2008.1500Published in Volume: 27 Issue 1: January 21, 2008PDF download

Hetero subunit interaction and RNA recognition of yeast tRNA (m7G46) methyltransferase synthesized in a wheat germ cell-free translation system

Yeast tRNA (m(7)G46) methyltransferase contains two protein subunits (Trm8 and Trm82). The enzyme catalyzes a methyl-transfer from S-adenosyl-L-methionine to the N(7) atom of guanine at position 46 in tRNA. We deviced synthesis of active Trm8-Trm82 heterodimer in a wheat germ cell-free translation system. When Trm8 or Trm82 mRNA were used for a synthesis, Trm8 or Trm82 protein could be synthesized. Upon mixing the synthesized Trm8 and Trm82 proteins, no active Trm8-Trm82 heterodimer was produced. Active Trm8-Trm82 heterodimer was only synthesized under conditions, in which both Trm8 and Trm82 mRNAs were co-translated. To address the RNA recognition mechanism of the Trm8-Trm82 complex, we investigated methyl acceptance activities of eight truncated yeast tRNA(Phe) transcripts. In this meeting, we demonstrate that yeast Trm8-Trm82 has stricter recognition requirements for the tRNA molecule as compared to the bacterial enzyme, TrmB.

Crystal Structure of the Radical SAM Enzyme Catalyzing Tricyclic Modified Base Formation in tRNA

Wyosine and its derivatives, such as wybutosine, found in eukaryotic and archaeal tRNAs, are tricyclic hypermodified nucleosides. In eukaryotes, wybutosine exists exclusively in position 37, 3′-adjacent to the anticodon, of tRNA Phe, where it ensures correct translation by stabilizing the codon-anticodon base-pairing during the ribosomal decoding process. Recent studies revealed that the wyosine biosynthetic pathway consists of multistep enzymatic reactions starting from a guanosine residue. Among these steps, TYW1 catalyzes the second step to form the tricyclic ring structure, by cyclizing N 1-methylguanosine. In this study, we solved the crystal structure of TYW1 from Methanocaldococcus jannaschii at 2.4 Å resolution. TYW1 assumes an incomplete TIM barrel with (α/β) 6 topology, which closely resembles the reported structures of radical SAM enzymes. Hence, TYW1 was considered to catalyze the cyclization reaction by utilizing the radical intermediate. Comparison with other radical SAM enzymes allowed us to build a model structure complexed with S-adenosylmethionine and two [4Fe-4S] clusters. Mutational analyses in yeast supported the validity of this complex model structure, which provides a structural insight into the radical reaction involving two [4Fe-4S] clusters to create a complex tricyclic base.

RNA recognition mechanism of eukaryote tRNA (m 7G46) methyltransferase (Trm8–Trm82 complex)

Yeast tRNA (m 7G46) methyltransferase contains two protein subunits (Trm8 and Trm82). To address the RNA recognition mechanism of the Trm8–Trm82 complex, we investigated methyl acceptance activities of eight truncated yeast tRNA Phe transcripts. Both the D-stem and T-stem structures were required for efficient methyl-transfer. To clarify the role of the D-stem structure, we tested four mutant transcripts, in which tertiary base pairs were disrupted. The tertiary base pairs were important but not essential for the methyl-transfer to yeast tRNA Phe transcript, suggesting that these base pairs support the induced fit of the G46 base into the catalytic pocket.

The complete nucleotide sequence and gene organization of the mitochondrial genome of the bumblebee, Bombus ignitus (Hymenoptera: Apidae)

The complete 16,434-bp nucleotide sequence of the mitogenome of the bumble bee, Bombus ignitus (Hymenoptera: Apidae), was determined. The genome contains the base composition and codon usage typical of metazoan mitogenomes. An unusual feature of the B. ignitus mitogenome is the presence of five tRNA-like structures: two each of the tRNA Leu(UUR) -like and tRNA Ser(AGN) -like sequences and one tRNA Phe -like sequence. These tRNA-like sequences have proper folding structures and anticodon sequences, but their functionality in their respective amino acid transfers remained uncertain. Among these sequences, the tRNA Leu(UUR) -like sequence and the tRNA Ser(AGN) -like sequence are seemingly located within the A+T-rich region. This tRNA Ser(AGN) -like sequence is highly unusual in that its sequence homology is very high compared to the tRNA Met of other insects, including Apis mellifera, but it contains the anticodon ACT, which designates it as tRNA Ser(AGN) . All PCG and rRNAs are conserved in positions observed most frequently in insect mitogenome structures, but the positions of the tRNAs are highly variable, presenting a new arrangement for an insect mitogenome. As a whole, the B. ignitus mitogenome contains the highest A+T content (86.9%) found in any of the complete insects mt sequences determined to date. All protein-coding sequences started with a typical ATN codon. Nine of the 13 PCGs have a complete termination codon (all TAA), but the remaining four genes terminate with the incomplete TA or T. All tRNAs have the typical clover-leaf structures of mt tRNAs, except for tRNA Ser(AGN) , in which the DHU arm forms a simple loop. All anticodons of B. ignitus tRNAs are identical to those of A. mellifera. In the A+T-rich region, a highly conserved sequence block that was previously described in Orthoptera and Diptera was also present. The stem-and-loop structures that may play a role in the initiation of mtDNA replication were also found in this region. Phylogenetic analysis among three corbiculate tribes, represented by Melipona bicolor (Meliponini), A. mellifera (Apini), and B. ignitus (Bombini), showed the closest relationship between M. bicolor and B. ignitus.

RNA binding small molecules: Studies on t-RNA binding by cytotoxic plant alkaloids berberine, palmatine and the comparison to ethidium

The interaction of two natural protoberberine plant alkaloids berberine and palmatine with t-RNA phe was studied using various biophysical techniques and the data was compared with the binding of the classical DNA intercalator, ethidium. The results of optical thermal melting, differential scanning calorimetry and circular dichroism characterized the native cloverleaf structure of t-RNA under the conditions of the study. The strong binding of the alkaloids and ethidium to t-RNA was revealed from the absorption and fluorescence studies. The salt dependence of the binding constants enabled the dissection of the binding free energy to electrostatic and non-electrostatic contributions. This analysis revealed a surprisingly large favourable component of the non-electrostatic contribution to the binding of these charged alkaloids and ethidium to t-RNA. Isothermal titration calorimetric studies revealed that the binding of both the alkaloids is driven by a moderately favourable enthalpy decrease and a moderately favourable entropy increase while that of ethidium is driven by a large favourable enthalpy decrease. Taken together, the results suggest that the binding of these alkaloid molecules on the t-RNA structure appears to be mostly by partial intercalation while ethidium intercalates to the t-RNA. These results reveal the molecular aspects on the interaction of these alkaloids to t-RNA.

The core domain of Aquifex aeolicus tRNA (m7G46) methyltransferase has the methyl-transfer activity to tRNA

Transfer RNA (m(7)G46) methyltransferase [TrmB] catalyses the transfer of methyl groups from S-adenosyl-L-methionine to the N(7)-atom of guanine at position 46 in tRNA. TrmB proteins from thermophilic bacteria such as Aquifex aeolicus have a long C-terminal region as compared to those from mesophilic bacteria. Further, N-terminal region observed in TrmB proteins from mesophiles is missing in A. aeolicus TrmB. Therefore, we considered that this distinct C-terminal region in A. aeolicus TrmB might compensate the N-terminal region in mesophile TrmB and function as a part of tRNA binding site. To confirm this idea, we deleted the C-terminal region by introduction of the stop codon at position 202. To our surprise, methyl-transfer assay using yeast tRNA(Phe) transcript clearly showed that the resultant mutant protein (Glu202Stop) had an enzymatic activity. Thus, the core domain of the A. aeolicus TrmB has a methyl-transfer activity.

Impact of forced selection of tRNAs on HIV-1 replication and genome stability highlight preferences for selection of certain tRNAs

Human immunodeficiency virus (HIV-1) exclusively selects tRNA Lys,3 as the primer for initiation of reverse transcription. How and why HIV-1 selects the tRNA is unresolved. To address this issue, we have generated HIV-1 in which the PBS was changed to be complementary to alternative tRNAs. In this study, we report on HIV-1 that have the PBS mutated to be complementary to tRNA Thr, tRNA Phe, tRNA Ser and tRNA Tyr. Virus with a PBS complementary to tRNA Thr grew slightly slower than the wild type virus and maintained the PBS for an extended culture period before finally reverting back to utilize tRNA Lys,3. In contrast, viruses with a PBS complementary to tRNA Phe or tRNA Ser rapidly reverted to utilize tRNA Lys,3 following limited in vitro replication, while a virus with a PBS complementary to tRNA Tyr had severely compromised infectivity and did not productively infect a continuous T cell line (SupT1) or human peripheral blood mononuclear cells (PBMC). Modification of the A-loop region to be complementary to tRNA Thr with the mutation in the PBS to be complementary to tRNA Thr resulted in a virus that could stably utilize this tRNA while the modification of the A-loop to be complementary to the anticodon of tRNA Ser did not allow the virus to stably utilize tRNA Ser. Modification of the A-loop region to be complementary to the anticodon of tRNA Phe severely impacted the replication of this virus. Finally, the modification of the A-loop region to be complementary to tRNA Tyr did not rescue the virus with a PBS complementary to tRNA Tyr. The results of these studies demonstrate the diverse effects that alteration of the PBS to force selection of alternative primers have on HIV-1 replication and provide a framework to understand the dynamics of primer selection.

Rapid In Situ Evolution of Nodulating Strains for Biserrula pelecinus L. through Lateral Transfer of a Symbiosis Island from the Original Mesorhizobial Inoculant

Diverse rhizobia able to nodulate Biserrula pelecinus evolved following in situ transfer of nodA and nifH from an inoculant to soil bacteria. Transfer of these chromosomal genes and the presence of an identical integrase gene adjacent to a Phe tRNA gene in both the inoculant and recipients indicate that there was lateral transfer of a symbiosis island.

Mitochondrial myopathy with exercise intolerance and retinal dystrophy in a sporadic patient with a G583A mutation in the mt tRNA phe gene

We describe a second patient with the 583G > A mutation in the tRNA phe gene of mitochondrial DNA (mtDNA). This 17-year-old girl had a mitochondrial myopathy with exercise intolerance and an asymptomatic retinopathy. Muscle investigations showed occasional ragged red fibers, 30% cytochrome c oxidase (COX)-negative fibers, and reduced activities of complex I + IV in the respiratory chain. The mutation was heteroplasmic (79%) in muscle but undetectable in other tissues. Analysis of single muscle fibers revealed a significantly higher level of mutated mtDNA in COX-negative fibers. Our study indicates that the 583G > A mutation is pathogenic and expands the clinical spectrum of this mutation.

A nature of conformational changes of yeast tRNA Phe: High hydrostatic pressure effects

We analysed conformational changes of yeast tRNA Phe induced by high hydrostatic pressure (HHP) measured by Fourier-transform infrared (FTIR) and fluorescence spectroscopies. High pressure influences RNA conformation without other cofactors, such as metal ions and salts. FTIR spectra of yeast tRNA Phe recorded at high hydrostatic pressure up to 13 kbar with and without magnesium ions showed a shift of the bands towards higher frequencies. That blue shift is due to an increase a higher energy of bonds as a result of shortening of hydrogen bonds followed by dehydration of tRNA. The fluorescence spectra of Y-base tRNA Phe at high pressure up to 3 kbar showed a decrease of the intensity band at 430 nm as a consequence of conformational rearrangement of the anticodon loop leading to exposure of Y-base side chain to the solution. We suggest that structural transition of nucleic acids is driven by the changes of water structure from tetrahedral to a cubic—like geometry induced by high pressure and, in consequence, due to economy of hydration.