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Special Issue "Functions of Transfer RNAs"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry, Molecular Biology and Biophysics".

Deadline for manuscript submissions: closed (30 April 2015)

Special Issue Editors

Guest Editor
Prof. Dr. Michael Ibba

Department of Microbiology and Center for RNA Biology, Ohio State University, Columbus, Ohio 43210-1292, USA
Website | E-Mail
Fax: +1 614 292 8120
Interests: translation; the genetic code; quality control; tRNA biology; microbial; stress response
Guest Editor
Prof. Dr. Constantinos Stathopoulos

Department of Biochemistry, School of Medicine, University of Patras, 1 Asklipiou st., 26504 Patras, Greece
Website | E-Mail
Fax: +30 2610 969167
Interests: tRNA; mRNA; riboswitches; antibiotics; aminoacyl-tRNA synthetases; ribonucleases; translation; ribosome; tRFs

Special Issue Information

Dear Colleagues,

Transfer RNA (tRNA) has played a key role in the field of molecular biology since its critical role in translating the genetic code started to emerge over 50 years ago. More recently, renewed interest in tRNA biology has come from all manor of fields including high resolution structure/function studies of the ribosome, the role of genetic recoding in synthetic biology, and a broad scope of medical advances from antibiotic resistance to cancer biology. These wide-ranging interests will all be represented at the 25th tRNA workshop that will be held in Greece in September 2014. This will mark the 50th anniversary of the tRNA meeting, and to coincide with this momentous event, we will assemble a series of review and research articles on the many Functions of tRNAs. The articles in this special issue of IJMS will cover a broad range of topics from tRNA synthesis and maturation, to the evolution of the genetic code, translation and human disease, providing an ideal resource for those interested in learning more about the latest developments in tRNA biology.

Prof. Dr. Michael Ibba
Prof. Dr. Constantinos Stathopoulos
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs).

Keywords

  • transfer RNA
  • translation
  • the genetic code
  • aminoacyl-tRNA synthesis
  • protein synthesis
  • tRNA-dependent biosynthesis
  • tRNA-dependent regulation

Related Special Issue

Published Papers (20 papers)

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Research

Jump to: Review

Open AccessArticle Distribution of ADAT-Dependent Codons in the Human Transcriptome
Int. J. Mol. Sci. 2015, 16(8), 17303-17314; doi:10.3390/ijms160817303
Received: 30 April 2015 / Revised: 2 July 2015 / Accepted: 6 July 2015 / Published: 29 July 2015
Cited by 2 | PDF Full-text (5450 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nucleotide modifications in the anticodons of transfer RNAs (tRNA) play a central role in translation efficiency, fidelity, and regulation of translation, but, for most of these modifications, the details of their function remain unknown. The heterodimeric adenosine deaminases acting on tRNAs (ADAT2-ADAT3, or
[...] Read more.
Nucleotide modifications in the anticodons of transfer RNAs (tRNA) play a central role in translation efficiency, fidelity, and regulation of translation, but, for most of these modifications, the details of their function remain unknown. The heterodimeric adenosine deaminases acting on tRNAs (ADAT2-ADAT3, or ADAT) are enzymes present in eukaryotes that convert adenine (A) to inosine (I) in the first anticodon base (position 34) by hydrolytic deamination. To explore the influence of ADAT activity on mammalian translation, we have characterized the human transcriptome and proteome in terms of frequency and distribution of ADAT-related codons. Eight different tRNAs can be modified by ADAT and, once modified, these tRNAs will recognize NNC, NNU and NNA codons, but not NNG codons. We find that transcripts coding for proteins highly enriched in these eight amino acids (ADAT-aa) are specifically enriched in NNC, NNU and NNA codons. We also show that the proteins most enriched in ADAT-aa are composed preferentially of threonine, alanine, proline, and serine (TAPS). We propose that the enrichment in ADAT-codons in these proteins is due to the similarities in the codons that correspond to TAPS. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Figures

Open AccessArticle The UGG Isoacceptor of tRNAPro Is Naturally Prone to Frameshifts
Int. J. Mol. Sci. 2015, 16(7), 14866-14883; doi:10.3390/ijms160714866
Received: 30 April 2015 / Revised: 23 June 2015 / Accepted: 24 June 2015 / Published: 1 July 2015
Cited by 1 | PDF Full-text (1627 KB) | HTML Full-text | XML Full-text
Abstract
Native tRNAs often contain post-transcriptional modifications to the wobble position to expand the capacity of reading the genetic code. Some of these modifications, due to the ability to confer imperfect codon-anticodon pairing at the wobble position, can induce a high propensity for tRNA
[...] Read more.
Native tRNAs often contain post-transcriptional modifications to the wobble position to expand the capacity of reading the genetic code. Some of these modifications, due to the ability to confer imperfect codon-anticodon pairing at the wobble position, can induce a high propensity for tRNA to shift into alternative reading frames. An example is the native UGG isoacceptor of E. coli tRNAPro whose wobble nucleotide U34 is post-transcriptionally modified to cmo5U34 to read all four proline codons (5ʹ-CCA, 5ʹ-CCC, 5ʹ-CCG, and 5ʹ-CCU). Because the pairing of the modified anticodon to CCC codon is particularly weak relative to CCA and CCG codons, this tRNA can readily shift into both the +1 and +2-frame on the slippery mRNA sequence CCC-CG. We show that the shift to the +2-frame is more dominant, driven by the higher stability of the codon-anticodon pairing at the wobble position. Kinetic analysis suggests that both types of shifts can occur during stalling of the tRNA in a post-translocation complex or during translocation from the A to the P-site. Importantly, while the +1-frame post complex is active for peptidyl transfer, the +2-frame complex is a poor peptidyl donor. Together with our recent work, we draw a mechanistic distinction between +1 and +2-frameshifts, showing that while the +1-shifts are suppressed by the additional post-transcriptionally modified m1G37 nucleotide in the anticodon loop, the +2-shifts are suppressed by the ribosome, supporting a role of the ribosome in the overall quality control of reading-frame maintenance. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Figures

Open AccessArticle A Moonlighting Human Protein Is Involved in Mitochondrial Import of tRNA
Int. J. Mol. Sci. 2015, 16(5), 9354-9367; doi:10.3390/ijms16059354
Received: 28 January 2015 / Revised: 2 April 2015 / Accepted: 15 April 2015 / Published: 24 April 2015
Cited by 2 | PDF Full-text (3592 KB) | HTML Full-text | XML Full-text
Abstract
In yeast Saccharomyces cerevisiae, ~3% of the lysine transfer RNA acceptor 1 (tRK1) pool is imported into mitochondria while the second isoacceptor, tRK2, fully remains in the cytosol. The mitochondrial function of tRK1 is suggested to boost mitochondrial translation under stress conditions.
[...] Read more.
In yeast Saccharomyces cerevisiae, ~3% of the lysine transfer RNA acceptor 1 (tRK1) pool is imported into mitochondria while the second isoacceptor, tRK2, fully remains in the cytosol. The mitochondrial function of tRK1 is suggested to boost mitochondrial translation under stress conditions. Strikingly, yeast tRK1 can also be imported into human mitochondria in vivo, and can thus be potentially used as a vector to address RNAs with therapeutic anti-replicative capacity into mitochondria of sick cells. Better understanding of the targeting mechanism in yeast and human is thus critical. Mitochondrial import of tRK1 in yeast proceeds first through a drastic conformational rearrangement of tRK1 induced by enolase 2, which carries this freight to the mitochondrial pre-lysyl-tRNA synthetase (preMSK). The latter may cross the mitochondrial membranes to reach the matrix where imported tRK1 could be used by the mitochondrial translation apparatus. This work focuses on the characterization of the complex that tRK1 forms with human enolases and their role on the interaction between tRK1 and human pre-lysyl-tRNA synthetase (preKARS2). Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Figures

Open AccessArticle Exploring the Balance between Folding and Functional Dynamics in Proteins and RNA
Int. J. Mol. Sci. 2015, 16(4), 6868-6889; doi:10.3390/ijms16046868
Received: 16 December 2014 / Revised: 11 March 2015 / Accepted: 11 March 2015 / Published: 26 March 2015
PDF Full-text (5337 KB) | HTML Full-text | XML Full-text
Abstract
As our understanding of biological dynamics continues to be refined, it is becoming clear that biomolecules can undergo transitions between ordered and disordered states as they execute functional processes. From a computational perspective, studying disorder events poses a challenge, as they typically occur
[...] Read more.
As our understanding of biological dynamics continues to be refined, it is becoming clear that biomolecules can undergo transitions between ordered and disordered states as they execute functional processes. From a computational perspective, studying disorder events poses a challenge, as they typically occur on long timescales, and the associated molecules are often large (i.e., hundreds of residues). These size and time requirements make it advantageous to use computationally inexpensive models to characterize large-scale dynamics, where more highly detailed models can provide information about individual sub-steps associated with function. To reduce computational demand, one often uses a coarse-grained representation of the molecule or a simplified description of the energetics. In order to use simpler models to identify transient disorder in RNA and proteins, it is imperative that these models can accurately capture structural fluctuations about folded configurations, as well as the overall stability of each molecule. Here, we explore a class of simplified model for which all non-hydrogen atoms are explicitly represented. We find that this model can provide a consistent description of protein folding and native-basin dynamics for several representative biomolecules. We additionally show that the native-basin fluctuations of tRNA and the ribosome are robust to variations in the model. Finally, the extended variable loop in tRNAIle is predicted to be very dynamic, which may facilitate biologically-relevant rearrangements. Together, this study provides a foundation that will aid in the application of simplified models to study disorder during function in ribonucleoprotein (RNP) assemblies. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessArticle Transfer RNA Methyltransferases from Thermoplasma acidophilum, a Thermoacidophilic Archaeon
Int. J. Mol. Sci. 2015, 16(1), 91-113; doi:10.3390/ijms16010091
Received: 7 November 2014 / Accepted: 12 December 2014 / Published: 23 December 2014
Cited by 2 | PDF Full-text (3004 KB) | HTML Full-text | XML Full-text
Abstract
We investigated tRNA methyltransferase activities in crude cell extracts from the thermoacidophilic archaeon Thermoplasma acidophilum. We analyzed the modified nucleosides in native initiator and elongator tRNAMet, predicted the candidate genes for the tRNA methyltransferases on the basis of the tRNA
[...] Read more.
We investigated tRNA methyltransferase activities in crude cell extracts from the thermoacidophilic archaeon Thermoplasma acidophilum. We analyzed the modified nucleosides in native initiator and elongator tRNAMet, predicted the candidate genes for the tRNA methyltransferases on the basis of the tRNAMet and tRNALeu sequences, and characterized Trm5, Trm1 and Trm56 by purifying recombinant proteins. We found that the Ta0997, Ta0931, and Ta0836 genes of T. acidophilum encode Trm1, Trm56 and Trm5, respectively. Initiator tRNAMet from T. acidophilum strain HO-62 contained G+, m1I, and m22G, which were not reported previously in this tRNA, and the m2G26 and m22G26 were formed by Trm1. In the case of elongator tRNAMet, our analysis showed that the previously unidentified G modification at position 26 was a mixture of m2G and m22G, and that they were also generated by Trm1. Furthermore, purified Trm1 and Trm56 could methylate the precursor of elongator tRNAMet, which has an intron at the canonical position. However, the speed of methyl-transfer by Trm56 to the precursor RNA was considerably slower than that to the mature transcript, which suggests that Trm56 acts mainly on the transcript after the intron has been removed. Moreover, cellular arrangements of the tRNA methyltransferases in T. acidophilum are discussed. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessArticle Effect of Hydrogen Peroxide on the Biosynthesis of Heme and Proteins: Potential Implications for the Partitioning of Glu-tRNAGlu between These Pathways
Int. J. Mol. Sci. 2014, 15(12), 23011-23023; doi:10.3390/ijms151223011
Received: 2 November 2014 / Revised: 24 November 2014 / Accepted: 4 December 2014 / Published: 11 December 2014
Cited by 2 | PDF Full-text (851 KB) | HTML Full-text | XML Full-text
Abstract
Glutamyl-tRNA (Glu-tRNAGlu) is the common substrate for both protein translation and heme biosynthesis via the C5 pathway. Under normal conditions, an adequate supply of this aminoacyl-tRNA is available to both pathways. However, under certain circumstances, Glu-tRNAGlu can become scarce,
[...] Read more.
Glutamyl-tRNA (Glu-tRNAGlu) is the common substrate for both protein translation and heme biosynthesis via the C5 pathway. Under normal conditions, an adequate supply of this aminoacyl-tRNA is available to both pathways. However, under certain circumstances, Glu-tRNAGlu can become scarce, resulting in competition between the two pathways for this aminoacyl-tRNA. In Acidithiobacillus ferrooxidans, glutamyl-tRNA synthetase 1 (GluRS1) is the main enzyme that synthesizes Glu-tRNAGlu. Previous studies have shown that GluRS1 is inactivated in vitro by hydrogen peroxide (H2O2). This raises the question as to whether H2O2 negatively affects in vivo GluRS1 activity in A. ferrooxidans and whether Glu-tRNAGlu distribution between the heme and protein biosynthesis processes may be affected by these conditions. To address this issue, we measured GluRS1 activity. We determined that GluRS1 is inactivated when cells are exposed to H2O2, with a concomitant reduction in intracellular heme level. The effects of H2O2 on the activity of purified glutamyl-tRNA reductase (GluTR), the key enzyme for heme biosynthesis, and on the elongation factor Tu (EF-Tu) were also measured. While exposing purified GluTR, the first enzyme of heme biosynthesis, to H2O2 resulted in its inactivation, the binding of glutamyl-tRNA to EF-Tu was not affected. Taken together, these data suggest that in A. ferrooxidans, the flow of glutamyl-tRNA is diverted from heme biosynthesis towards protein synthesis under oxidative stress conditions. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessArticle RNase P RNA from the Recently Evolved Plastid of Paulinella and from Algae
Int. J. Mol. Sci. 2014, 15(11), 20859-20875; doi:10.3390/ijms151120859
Received: 9 October 2014 / Revised: 28 October 2014 / Accepted: 3 November 2014 / Published: 13 November 2014
PDF Full-text (1808 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The RNase P RNA catalytic subunit (RPR) encoded in some plastids has been found to be functionally defective. The amoeba Paulinella chromatophora contains an organelle (chromatophore) that is derived from the recent endosymbiotic acquisition of a cyanobacterium, and therefore represents a model of
[...] Read more.
The RNase P RNA catalytic subunit (RPR) encoded in some plastids has been found to be functionally defective. The amoeba Paulinella chromatophora contains an organelle (chromatophore) that is derived from the recent endosymbiotic acquisition of a cyanobacterium, and therefore represents a model of the early steps in the acquisition of plastids. In contrast with plastid RPRs the chromatophore RPR retains functionality similar to the cyanobacterial enzyme. The chromatophore RPR sequence deviates from consensus at some positions but those changes allow optimal activity compared with mutated chromatophore RPR with the consensus sequence. We have analyzed additional RPR sequences identifiable in plastids and have found that it is present in all red algae and in several prasinophyte green algae. We have assayed in vitro a subset of the plastid RPRs not previously analyzed and confirm that these organelle RPRs lack RNase P activity in vitro. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)

Review

Jump to: Research

Open AccessReview MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery
Int. J. Mol. Sci. 2015, 16(7), 15872-15902; doi:10.3390/ijms160715872
Received: 6 June 2015 / Revised: 7 July 2015 / Accepted: 8 July 2015 / Published: 13 July 2015
Cited by 3 | PDF Full-text (2963 KB) | HTML Full-text | XML Full-text
Abstract
While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations
[...] Read more.
While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades. We then review the background of tRNA molecules, aminoacyl-tRNA synthetases, and current state of the art MD simulation techniques for those who may be unfamiliar with any of those fields. Recent MD simulations of tRNA dynamics and folding and of aminoacyl-tRNA synthetase dynamics and mechanistic characterizations are discussed. We highlight the recent successes and discuss how important questions can be addressed using current MD simulations techniques. We also outline several natural next steps for computational studies of AARS:tRNA complexes. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Figures

Open AccessReview Structural Insights into tRNA Dynamics on the Ribosome
Int. J. Mol. Sci. 2015, 16(5), 9866-9895; doi:10.3390/ijms16059866
Received: 27 March 2015 / Revised: 21 April 2015 / Accepted: 22 April 2015 / Published: 30 April 2015
Cited by 5 | PDF Full-text (11963 KB) | HTML Full-text | XML Full-text
Abstract
High-resolution structures at different stages, as well as biochemical, single molecule and computational approaches have highlighted the elasticity of tRNA molecules when bound to the ribosome. It is well acknowledged that the inherent structural flexibility of the tRNA lies at the heart of
[...] Read more.
High-resolution structures at different stages, as well as biochemical, single molecule and computational approaches have highlighted the elasticity of tRNA molecules when bound to the ribosome. It is well acknowledged that the inherent structural flexibility of the tRNA lies at the heart of the protein synthesis process. Here, we review the recent advances and describe considerations that the conformational changes of the tRNA molecules offer about the mechanisms grounded in translation. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessReview Interaction of tRNA with Eukaryotic Ribosome
Int. J. Mol. Sci. 2015, 16(4), 7173-7194; doi:10.3390/ijms16047173
Received: 8 December 2014 / Revised: 20 March 2015 / Accepted: 23 March 2015 / Published: 30 March 2015
Cited by 3 | PDF Full-text (3742 KB) | HTML Full-text | XML Full-text
Abstract
This paper is a review of currently available data concerning interactions of tRNAs with the eukaryotic ribosome at various stages of translation. These data include the results obtained by means of cryo-electron microscopy and X-ray crystallography applied to various model ribosomal complexes, site-directed
[...] Read more.
This paper is a review of currently available data concerning interactions of tRNAs with the eukaryotic ribosome at various stages of translation. These data include the results obtained by means of cryo-electron microscopy and X-ray crystallography applied to various model ribosomal complexes, site-directed cross-linking with the use of tRNA derivatives bearing chemically or photochemically reactive groups in the CCA-terminal fragment and chemical probing of 28S rRNA in the region of the peptidyl transferase center. Similarities and differences in the interactions of tRNAs with prokaryotic and eukaryotic ribosomes are discussed with concomitant consideration of the extent of resemblance between molecular mechanisms of translation in eukaryotes and bacteria. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessReview Aminoacyl-tRNA Synthetase Complexes in Evolution
Int. J. Mol. Sci. 2015, 16(3), 6571-6594; doi:10.3390/ijms16036571
Received: 15 December 2014 / Revised: 17 February 2015 / Accepted: 11 March 2015 / Published: 23 March 2015
Cited by 10 | PDF Full-text (2025 KB) | HTML Full-text | XML Full-text
Abstract
Aminoacyl-tRNA synthetases are essential enzymes for interpreting the genetic code. They are responsible for the proper pairing of codons on mRNA with amino acids. In addition to this canonical, translational function, they are also involved in the control of many cellular pathways essential
[...] Read more.
Aminoacyl-tRNA synthetases are essential enzymes for interpreting the genetic code. They are responsible for the proper pairing of codons on mRNA with amino acids. In addition to this canonical, translational function, they are also involved in the control of many cellular pathways essential for the maintenance of cellular homeostasis. Association of several of these enzymes within supramolecular assemblies is a key feature of organization of the translation apparatus in eukaryotes. It could be a means to control their oscillation between translational functions, when associated within a multi-aminoacyl-tRNA synthetase complex (MARS), and nontranslational functions, after dissociation from the MARS and association with other partners. In this review, we summarize the composition of the different MARS described from archaea to mammals, the mode of assembly of these complexes, and their roles in maintenance of cellular homeostasis. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Figures

Open AccessReview Recent Developments of Engineered Translational Machineries for the Incorporation of Non-Canonical Amino Acids into Polypeptides
Int. J. Mol. Sci. 2015, 16(3), 6513-6531; doi:10.3390/ijms16036513
Received: 14 January 2015 / Revised: 13 March 2015 / Accepted: 16 March 2015 / Published: 20 March 2015
Cited by 3 | PDF Full-text (2092 KB) | HTML Full-text | XML Full-text
Abstract
Genetic code expansion and reprogramming methodologies allow us to incorporate non-canonical amino acids (ncAAs) bearing various functional groups, such as fluorescent groups, bioorthogonal functional groups, and post-translational modifications, into a desired position or multiple positions in polypeptides both in vitro and in vivo
[...] Read more.
Genetic code expansion and reprogramming methodologies allow us to incorporate non-canonical amino acids (ncAAs) bearing various functional groups, such as fluorescent groups, bioorthogonal functional groups, and post-translational modifications, into a desired position or multiple positions in polypeptides both in vitro and in vivo. In order to efficiently incorporate a wide range of ncAAs, several methodologies have been developed, such as orthogonal aminoacyl-tRNA-synthetase (AARS)–tRNA pairs, aminoacylation ribozymes, frame-shift suppression of quadruplet codons, and engineered ribosomes. More recently, it has been reported that an engineered translation system specifically utilizes an artificially built genetic code and functions orthogonally to naturally occurring counterpart. In this review we summarize recent advances in the field of ribosomal polypeptide synthesis containing ncAAs. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Figures

Open AccessReview tRNA Biology in Mitochondria
Int. J. Mol. Sci. 2015, 16(3), 4518-4559; doi:10.3390/ijms16034518
Received: 19 November 2014 / Revised: 23 January 2015 / Accepted: 29 January 2015 / Published: 27 February 2015
Cited by 10 | PDF Full-text (1796 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mitochondria are the powerhouses of eukaryotic cells. They are considered as semi-autonomous because they have retained genomes inherited from their prokaryotic ancestor and host fully functional gene expression machineries. These organelles have attracted considerable attention because they combine bacterial-like traits with novel features
[...] Read more.
Mitochondria are the powerhouses of eukaryotic cells. They are considered as semi-autonomous because they have retained genomes inherited from their prokaryotic ancestor and host fully functional gene expression machineries. These organelles have attracted considerable attention because they combine bacterial-like traits with novel features that evolved in the host cell. Among them, mitochondria use many specific pathways to obtain complete and functional sets of tRNAs as required for translation. In some instances, tRNA genes have been partially or entirely transferred to the nucleus and mitochondria require precise import systems to attain their pool of tRNAs. Still, tRNA genes have also often been maintained in mitochondria. Their genetic arrangement is more diverse than previously envisaged. The expression and maturation of mitochondrial tRNAs often use specific enzymes that evolved during eukaryote history. For instance many mitochondria use a eukaryote-specific RNase P enzyme devoid of RNA. The structure itself of mitochondrial encoded tRNAs is also very diverse, as e.g., in Metazoan, where tRNAs often show non canonical or truncated structures. As a result, the translational machinery in mitochondria evolved adapted strategies to accommodate the peculiarities of these tRNAs, in particular simplified identity rules for their aminoacylation. Here, we review the specific features of tRNA biology in mitochondria from model species representing the major eukaryotic groups, with an emphasis on recent research on tRNA import, maturation and aminoacylation. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessReview Experimental Confirmation of a Whole Set of tRNA Molecules in Two Archaeal Species
Int. J. Mol. Sci. 2015, 16(1), 2187-2203; doi:10.3390/ijms16012187
Received: 26 November 2014 / Accepted: 14 January 2015 / Published: 20 January 2015
PDF Full-text (1467 KB) | HTML Full-text | XML Full-text
Abstract
Based on the genomic sequences for most archaeal species, only one tRNA gene (isodecoder) is predicted for each triplet codon. This observation promotes analysis of a whole set of tRNA molecules and actual splicing patterns of interrupted tRNA in one organism. The entire
[...] Read more.
Based on the genomic sequences for most archaeal species, only one tRNA gene (isodecoder) is predicted for each triplet codon. This observation promotes analysis of a whole set of tRNA molecules and actual splicing patterns of interrupted tRNA in one organism. The entire genomic sequences of two Creanarchaeota, Aeropyrum pernix and Sulfolobus tokodaii, were determined approximately 15 years ago. In these genome datasets, 47 and 46 tRNA genes were detected, respectively. Among them, 14 and 24 genes, respectively, were predicted to be interrupted tRNA genes. To confirm the actual transcription of these predicted tRNA genes and identify the actual splicing patterns of the predicted interrupted tRNA molecules, RNA samples were prepared from each archaeal species and used to synthesize cDNA molecules with tRNA sequence-specific primers. Comparison of the nucleotide sequences of cDNA clones representing unspliced and spliced forms of interrupted tRNA molecules indicated that some introns were located at positions other than one base 3' from anticodon region and that bulge-helix-bulge structures were detected around the actual splicing sites in each interrupted tRNA molecule. Whole-set analyses of tRNA molecules revealed that the archaeal tRNA splicing mechanism may be essential for efficient splicing of all tRNAs produced from interrupted tRNA genes in these archaea. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessReview Surveillance and Cleavage of Eukaryotic tRNAs
Int. J. Mol. Sci. 2015, 16(1), 1873-1893; doi:10.3390/ijms16011873
Received: 19 December 2014 / Accepted: 9 January 2015 / Published: 15 January 2015
Cited by 8 | PDF Full-text (1327 KB) | HTML Full-text | XML Full-text
Abstract
Beyond their central role in protein synthesis, transfer RNAs (tRNAs) have many other crucial functions. This includes various roles in the regulation of gene expression, stress responses, metabolic processes and priming reverse transcription. In the RNA world, tRNAs are, with ribosomal RNAs, among
[...] Read more.
Beyond their central role in protein synthesis, transfer RNAs (tRNAs) have many other crucial functions. This includes various roles in the regulation of gene expression, stress responses, metabolic processes and priming reverse transcription. In the RNA world, tRNAs are, with ribosomal RNAs, among the most stable molecules. Nevertheless, they are not eternal. As key elements of cell function, tRNAs need to be continuously quality-controlled. Two tRNA surveillance pathways have been identified. They act on hypo-modified or mis-processed pre-tRNAs and on mature tRNAs lacking modifications. A short overview of these two pathways will be presented here. Furthermore, while the exoribonucleases acting in these pathways ultimately lead to complete tRNA degradation, numerous tRNA-derived fragments (tRFs) are present within a cell. These cleavage products of tRNAs now potentially emerge as a new class of small non-coding RNAs (sncRNAs) and are suspected to have important regulatory functions. The tRFs are evolutionarily widespread and created by cleavage at different positions by various endonucleases. Here, we review our present knowledge on the biogenesis and function of tRFs in various organisms. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Figures

Open AccessReview tRNAs as Antibiotic Targets
Int. J. Mol. Sci. 2015, 16(1), 321-349; doi:10.3390/ijms16010321
Received: 25 November 2014 / Accepted: 19 December 2014 / Published: 25 December 2014
Cited by 4 | PDF Full-text (1161 KB) | HTML Full-text | XML Full-text
Abstract
Transfer RNAs (tRNAs) are central players in the protein translation machinery and as such are prominent targets for a large number of natural and synthetic antibiotics. This review focuses on the role of tRNAs in bacterial antibiosis. We will discuss examples of antibiotics
[...] Read more.
Transfer RNAs (tRNAs) are central players in the protein translation machinery and as such are prominent targets for a large number of natural and synthetic antibiotics. This review focuses on the role of tRNAs in bacterial antibiosis. We will discuss examples of antibiotics that target multiple stages in tRNA biology from tRNA biogenesis and modification, mature tRNAs, aminoacylation of tRNA as well as prevention of proper tRNA function by small molecules binding to the ribosome. Finally, the role of deacylated tRNAs in the bacterial “stringent response” mechanism that can lead to bacteria displaying antibiotic persistence phenotypes will be discussed. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessReview From End to End: tRNA Editing at 5'- and 3'-Terminal Positions
Int. J. Mol. Sci. 2014, 15(12), 23975-23998; doi:10.3390/ijms151223975
Received: 16 November 2014 / Revised: 10 December 2014 / Accepted: 16 December 2014 / Published: 22 December 2014
Cited by 7 | PDF Full-text (1440 KB) | HTML Full-text | XML Full-text
Abstract
During maturation, tRNA molecules undergo a series of individual processing steps, ranging from exo- and endonucleolytic trimming reactions at their 5'- and 3'-ends, specific base modifications and intron removal to the addition of the conserved 3'-terminal CCA sequence. Especially in mitochondria, this plethora
[...] Read more.
During maturation, tRNA molecules undergo a series of individual processing steps, ranging from exo- and endonucleolytic trimming reactions at their 5'- and 3'-ends, specific base modifications and intron removal to the addition of the conserved 3'-terminal CCA sequence. Especially in mitochondria, this plethora of processing steps is completed by various editing events, where base identities at internal positions are changed and/or nucleotides at 5'- and 3'-ends are replaced or incorporated. In this review, we will focus predominantly on the latter reactions, where a growing number of cases indicate that these editing events represent a rather frequent and widespread phenomenon. While the mechanistic basis for 5'- and 3'-end editing differs dramatically, both reactions represent an absolute requirement for generating a functional tRNA. Current in vivo and in vitro model systems support a scenario in which these highly specific maturation reactions might have evolved out of ancient promiscuous RNA polymerization or quality control systems. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Figures

Open AccessReview Regulation of Angiogenesis by Aminoacyl-tRNA Synthetases
Int. J. Mol. Sci. 2014, 15(12), 23725-23748; doi:10.3390/ijms151223725
Received: 17 November 2014 / Revised: 11 December 2014 / Accepted: 12 December 2014 / Published: 19 December 2014
Cited by 5 | PDF Full-text (1610 KB) | HTML Full-text | XML Full-text
Abstract
In addition to their canonical roles in translation the aminoacyl-tRNA synthetases (ARSs) have developed secondary functions over the course of evolution. Many of these activities are associated with cellular survival and nutritional stress responses essential for homeostatic processes in higher eukaryotes. In particular,
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In addition to their canonical roles in translation the aminoacyl-tRNA synthetases (ARSs) have developed secondary functions over the course of evolution. Many of these activities are associated with cellular survival and nutritional stress responses essential for homeostatic processes in higher eukaryotes. In particular, six ARSs and one associated factor have documented functions in angiogenesis. However, despite their connection to this process, the ARSs are mechanistically distinct and exhibit a range of positive or negative effects on aspects of endothelial cell migration, proliferation, and survival. This variability is achieved through the appearance of appended domains and interplay with inflammatory pathways not found in prokaryotic systems. Complete knowledge of the non-canonical functions of ARSs is necessary to understand the mechanisms underlying the physiological regulation of angiogenesis. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessReview tRNA Modification Enzymes GidA and MnmE: Potential Role in Virulence of Bacterial Pathogens
Int. J. Mol. Sci. 2014, 15(10), 18267-18280; doi:10.3390/ijms151018267
Received: 3 September 2014 / Revised: 2 October 2014 / Accepted: 8 October 2014 / Published: 10 October 2014
Cited by 8 | PDF Full-text (671 KB) | HTML Full-text | XML Full-text
Abstract
Transfer RNA (tRNA) is an RNA molecule that carries amino acids to the ribosomes for protein synthesis. These tRNAs function at the peptidyl (P) and aminoacyl (A) binding sites of the ribosome during translation, with each codon being recognized by a specific tRNA.
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Transfer RNA (tRNA) is an RNA molecule that carries amino acids to the ribosomes for protein synthesis. These tRNAs function at the peptidyl (P) and aminoacyl (A) binding sites of the ribosome during translation, with each codon being recognized by a specific tRNA. Due to this specificity, tRNA modification is essential for translational efficiency. Many enzymes have been implicated in the modification of bacterial tRNAs, and these enzymes may complex with one another or interact individually with the tRNA. Approximately, 100 tRNA modification enzymes have been identified with glucose-inhibited division (GidA) protein and MnmE being two of the enzymes studied. In Escherichia coli and Salmonella, GidA and MnmE bind together to form a functional complex responsible for the proper biosynthesis of 5-methylaminomethyl-2-thiouridine (mnm5s2U34) of tRNAs. Studies have implicated this pathway in a major pathogenic regulatory mechanism as deletion of gidA and/or mnmE has attenuated several bacterial pathogens like Salmonella enterica serovar Typhimurium, Pseudomonas syringae, Aeromonas hydrophila, and many others. In this review, we summarize the potential role of the GidA/MnmE tRNA modification pathway in bacterial virulence, interactions with the host, and potential therapeutic strategies resulting from a greater understanding of this regulatory mechanism. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
Open AccessReview Structures and Functions of Qβ Replicase: Translation Factors beyond Protein Synthesis
Int. J. Mol. Sci. 2014, 15(9), 15552-15570; doi:10.3390/ijms150915552
Received: 7 August 2014 / Revised: 27 August 2014 / Accepted: 29 August 2014 / Published: 2 September 2014
Cited by 1 | PDF Full-text (1239 KB) | HTML Full-text | XML Full-text
Abstract
Qβ replicase is a unique RNA polymerase complex, comprising Qβ virus-encoded RNA-dependent RNA polymerase (the catalytic β-subunit) and three host-derived factors: translational elongation factor (EF) -Tu, EF-Ts and ribosomal protein S1. For almost fifty years, since the isolation of Qβ replicase, there have
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Qβ replicase is a unique RNA polymerase complex, comprising Qβ virus-encoded RNA-dependent RNA polymerase (the catalytic β-subunit) and three host-derived factors: translational elongation factor (EF) -Tu, EF-Ts and ribosomal protein S1. For almost fifty years, since the isolation of Qβ replicase, there have been several unsolved, important questions about the mechanism of RNA polymerization by Qβ replicase. Especially, the detailed functions of the host factors, EF-Tu, EF-Ts, and S1, in Qβ replicase, which are all essential in the Escherichia coli (E. coli) host for protein synthesis, had remained enigmatic, due to the absence of structural information about Qβ replicase. In the last five years, the crystal structures of the core Qβ replicase, consisting of the β-subunit, EF-Tu and Ts, and those of the core Qβ replicase representing RNA polymerization, have been reported. Recently, the structure of Qβ replicase comprising the β-subunit, EF-Tu, EF-Ts and the N-terminal half of S1, which is capable of initiating Qβ RNA replication, has also been reported. In this review, based on the structures of Qβ replicase, we describe our current understanding of the alternative functions of the host translational elongation factors and ribosomal protein S1 in Qβ replicase as replication factors, beyond their established functions in protein synthesis. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
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