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Advanced Research of tRNA

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

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 6024

Special Issue Editor


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Guest Editor
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Sciences, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland
Interests: therapeutic nucleic acids; siRNAs; antisense oligonucleotides; CRISPR/Cas9 gene editing; tRNA; epitranscriptomics; nucleoside modifications; nucleoside modifying enzymes; genetic code decoding; codon-anticodon interaction; oxidative tRNA damage; biotechnology and recombinant proteins
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Special Issue Information

Dear Colleagues,

The second half of the 19th and the 20th centuries were marked by great discoveries in the field of nucleic acids, which ushered in a new era in the development of biological sciences. The discovery of nucleic acids, the determination of their functions and structures, the deciphering of the genetic code, the identification of the first modified nucleosides in RNA, and much more have laid the foundation for modern molecular biology.

One of these great achievements was the discovery of transfer ribonucleic acid (tRNA). Exactly 65 years ago, in 1958, Mahlon B. Hoagland and Paul C. Zamecnik informed the scientific community of the discovery of an endogenous low-molecular-weight RNA fraction that acts as an intermediate in the movement of amino acids from the ATP-activated state to the newly formed protein. Confirmation of the presence of an adapter molecule that serves as a physical link between the genetic information and an amino acid sequence of a growing polypeptide chain was an excellent explanation for the flow of genetic information in biological systems.

On the occasion of the anniversary of tRNA, we would like to commemorate its history, but more importantly, highlight the great progress that has been made in the study of the structure, function, and chemical modifications of nucleosides in tRNA. This Special Issue of the International Journal of Molecular Sciences focuses on advanced research in the field of tRNA, particularly tRNA biology, the development of new modifications and their effects on tRNA functions, tRNA-modifying enzymes, the effects of stress conditions on the presence or absence of nucleoside modifications in tRNA, and tRNA damage and its impact on cellular health or disease. We invite and encourage scientists to submit original research manuscripts or review articles discussing the latest aspects of tRNA research. We hope to provide a useful compilation of the latest developments in tRNA biology.

Dr. Małgorzata Sierant
Guest Editor

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Keywords

  • transfer ribonucleic acid, tRNA
  • tRNA structure
  • tRNA maturation
  • tRNA modification
  • epitranscriptomics
  • tRNA function
  • codon–anticodon recognition
  • translation
  • decoding the genetic code
  • tRNA damages

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Published Papers (3 papers)

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Research

26 pages, 4613 KiB  
Article
Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation
by Daisuke Ando, Sherif Rashad, Thomas J. Begley, Hidenori Endo, Masashi Aoki, Peter C. Dedon and Kuniyasu Niizuma
Int. J. Mol. Sci. 2025, 26(2), 706; https://doi.org/10.3390/ijms26020706 - 15 Jan 2025
Cited by 2 | Viewed by 2063
Abstract
The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as [...] Read more.
The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as well as codon optimality across seven mouse tissues. Our analysis revealed distinct enrichment patterns of tRNA modifications in different tissues. Queuosine (Q) tRNA modification was most enriched in the brain compared to other tissues, while mitochondrial tRNA modifications and tRNA expression were highest in the heart. Using this observation, we synthesized, and delivered in vivo, codon-mutated EGFP for Q-codons, where the C-ending Q-codons were replaced with U-ending codons. The protein levels of mutant EGFP were downregulated in liver, which is poor in Q, while in brain EGFP, levels did not change. These data show that understanding tRNA modification enrichments across tissues is not only essential for understanding codon decoding and bias but can also be utilized for optimizing gene and mRNA therapeutics to be more tissue-, cell-, or condition-specific. Full article
(This article belongs to the Special Issue Advanced Research of tRNA)
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24 pages, 4541 KiB  
Article
Studies on the Oxidative Damage of the Wobble 5-Methylcarboxymethyl-2-Thiouridine in the tRNA of Eukaryotic Cells with Disturbed Homeostasis of the Antioxidant System
by Malgorzata Sierant, Rafal Szewczyk, Agnieszka Dziergowska, Karolina Krolewska-Golinska, Patrycja Szczupak, Przemyslaw Bernat and Barbara Nawrot
Int. J. Mol. Sci. 2024, 25(22), 12336; https://doi.org/10.3390/ijms252212336 - 17 Nov 2024
Viewed by 1536
Abstract
We have previously shown that 2-thiouridine (S2U), either as a single nucleoside or as an element of RNA chain, is effectively desulfurized under applied in vitro oxidative conditions. The chemically induced desulfuration of S2U resulted in two products: 4-pyrimidinone nucleoside (H2U) and uridine [...] Read more.
We have previously shown that 2-thiouridine (S2U), either as a single nucleoside or as an element of RNA chain, is effectively desulfurized under applied in vitro oxidative conditions. The chemically induced desulfuration of S2U resulted in two products: 4-pyrimidinone nucleoside (H2U) and uridine (U). Recently, we investigated whether the desulfuration of S2U is a natural process that also occurs in the cells exposed to oxidative stress or whether it only occurs in the test tube during chemical reactions with oxidants at high concentrations. Using different types of eukaryotic cells, such as baker’s yeast, human cancer cells, or modified HEK293 cells with an impaired antioxidant system, we confirmed that 5-substituted 2-thiouridines are oxidatively desulfurized in the wobble position of the anticodon of some tRNAs. The quantitative LC-MS/MS-MRMhr analysis of the nucleoside mixtures obtained from the hydrolyzed tRNA revealed the presence of the desulfuration products of mcm5S2U: mcm5H2U and mcm5U modifications. We also observed some amounts of immature cm5S2U, cm5H2U and cm5U products, which may have indicated a disruption of the enzymatic modification pathway at the C5 position of 2-thiouridine. The observed process, which was triggered by oxidative stress in the living cells, could impair the function of 2-thiouridine-containing tRNAs and alter the translation of genetic information. Full article
(This article belongs to the Special Issue Advanced Research of tRNA)
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22 pages, 3751 KiB  
Article
Temperature-Dependent tRNA Modifications in Bacillales
by Anne Hoffmann, Christian Lorenz, Jörg Fallmann, Philippe Wolff, Antony Lechner, Heike Betat, Mario Mörl and Peter F. Stadler
Int. J. Mol. Sci. 2024, 25(16), 8823; https://doi.org/10.3390/ijms25168823 - 13 Aug 2024
Cited by 1 | Viewed by 1696
Abstract
Transfer RNA (tRNA) modifications are essential for the temperature adaptation of thermophilic and psychrophilic organisms as they control the rigidity and flexibility of transcripts. To further understand how specific tRNA modifications are adjusted to maintain functionality in response to temperature fluctuations, we investigated [...] Read more.
Transfer RNA (tRNA) modifications are essential for the temperature adaptation of thermophilic and psychrophilic organisms as they control the rigidity and flexibility of transcripts. To further understand how specific tRNA modifications are adjusted to maintain functionality in response to temperature fluctuations, we investigated whether tRNA modifications represent an adaptation of bacteria to different growth temperatures (minimal, optimal, and maximal), focusing on closely related psychrophilic (P. halocryophilus and E. sibiricum), mesophilic (B. subtilis), and thermophilic (G. stearothermophilus) Bacillales. Utilizing an RNA sequencing approach combined with chemical pre-treatment of tRNA samples, we systematically profiled dihydrouridine (D), 4-thiouridine (s4U), 7-methyl-guanosine (m7G), and pseudouridine (Ψ) modifications at single-nucleotide resolution. Despite their close relationship, each bacterium exhibited a unique tRNA modification profile. Our findings revealed increased tRNA modifications in the thermophilic bacterium at its optimal growth temperature, particularly showing elevated levels of s4U8 and Ψ55 modifications compared to non-thermophilic bacteria, indicating a temperature-dependent regulation that may contribute to thermotolerance. Furthermore, we observed higher levels of D modifications in psychrophilic and mesophilic bacteria, indicating an adaptive strategy for cold environments by enhancing local flexibility in tRNAs. Our method demonstrated high effectiveness in identifying tRNA modifications compared to an established tool, highlighting its potential for precise tRNA profiling studies. Full article
(This article belongs to the Special Issue Advanced Research of tRNA)
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