Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 706 - 706

Published: Jan. 15, 2025

The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role fine-tuning via codon decoding at tissue or cell levels remains incomplete. We analyzed expression and modifications well optimality across seven mouse tissues. analysis revealed distinct enrichment patterns different Queuosine (Q) modification was most enriched brain compared to other tissues, while mitochondrial were highest heart. Using this observation, we synthesized, delivered vivo, codon-mutated EGFP for Q-codons, where C-ending Q-codons replaced with U-ending codons. protein mutant downregulated liver, which is poor Q, EGFP, did not change. These data show that understanding enrichments tissues only essential bias but can also be utilized optimizing gene therapeutics more tissue-, cell-, condition-specific.

Language: Английский

Metabolism Meets Translation: Dietary and Metabolic Influences on tRNA Modifications and Codon Biased Translation

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2025, Volume and Issue: 16(2)

Published: March 1, 2025

ABSTRACT Transfer RNA (tRNA) is not merely a passive carrier of amino acids, but an active regulator mRNA translation controlling codon bias and optimality. The synthesis various tRNA modifications regulated by many “writer” enzymes, which utilize substrates from metabolic pathways or dietary sources. Metabolic bioenergetic pathways, such as one‐carbon (1C) metabolism the tricarboxylic acid (TCA) cycle produce essential for synthesis, S‐Adenosyl methionine (SAM), sulfur species, α‐ketoglutarate (α‐KG). activity these can directly impact decoding via regulating levels. In this review, we discuss complex interactions between diet, metabolism, modifications, translation. We how nutrient availability, bioenergetics, intermediates modulate modification landscape to fine‐tune protein synthesis. Moreover, highlight dysregulation metabolic‐tRNA contributes disease pathogenesis, including cancer, disorders, neurodegenerative diseases. also new emerging field GlycoRNA biology drawing parallels glycobiology diseases guide future directions in area. Throughout our discussion, links specific their metabolic/dietary precursors, diseases, emphasizing importance metabolism‐centric view understanding pathologies. Future research should focus on uncovering interplay cellular contexts. Addressing gaps will into novel interventions.

Language: Английский

Structural Snapshots of Human tRNA Modifying Enzymes

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169106 - 169106

Published: April 1, 2025

Cells use a plethora of specialized enzymes to post-transcriptionally introduce chemical modifications into transfer RNA (tRNA) molecules. These contribute novel properties the affected nucleotides and are crucial for tRNA maturation process most other aspects biology. Whereas, some ubiquitous respective modifying conserved in all domains life, found only specific organisms, tRNAs or at positions tRNAs. Despite fact, that evolution has shaped tremendous variety modification cascades, clinical relevance patient-derived mutations recently led an increased interest set human enzymes. Over decades macromolecular crystallography immensely contributed understand enzymatic function molecular level. The advent high resolution single-particle cryo-EM structures several clinically relevant complex with more fundamental understanding mechanistic consequences disease-related mutations. Here, we aim provide comprehensive summary currently available experimentally determined

Language: Английский