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

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Deciphering the Diversity in Bacterial Transporters That Salvage Queuosine Precursors

Epigenomes, Journal Year: 2024, Volume and Issue: 8(2), P. 16 - 16

Published: April 25, 2024

Queuosine (Q) is a modification of the wobble base tRNA harboring GUN anticodons with roles in decoding accuracy and efficiency. Its synthesis complex multiple enzymatic steps, several pathway intermediates can be salvaged. The only two transporter families known to salvage Q precursors are QPTR/COG1738 QrtT/QueT. Analyses distribution genes human gut oral microbiota genomes have suggested that more remain found precursor exchanges must occur within structured microenvironments mammalian host. Using physical clustering fusion-based association genes, candidate for missing transporters were identified five tested experimentally by complementation assays Escherichia coli. Three encoding from three different Pfam families, ureide permease (PF07168) Acidobacteriota bacterium, hemolysin III family protein (PF03006) Bifidobacterium breve, Major Facilitator Superfamily (PF07690) Bartonella henselae, allow transport both preQ0 preQ1 this heterologous system. This work suggests many evolve precursors, reinforcing concept plasticity.

Language: Английский

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Queuosine tRNA Modification: Connecting the Microbiome to the Translatome

BioEssays, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

ABSTRACT Transfer RNA (tRNA) modifications play an important role in regulating mRNA translation at the codon level. tRNA can influence selection and optimality, thus shifting toward specific sets of mRNAs a dynamic manner. Queuosine (Q) is modification occurring wobble position. In eukaryotes, queuosine synthesized by tRNA‐guanine trans ‐glycosylase (TGT) complex, which incorporates nucleobase queuine (or Qbase) into guanine GUN anticodons. Queuine sourced from gut bacteria dietary intake. Q was recently shown to be critical for cellular responses oxidative mitochondrial stresses, as well its potential neurodegenerative diseases brain health. These unique features provide interesting insight regulation bacteria, health implications. this review, biology examined light recent literature nearly 4 decades research. Q's neuropsychiatric cancer highlighted discussed. Given interest Q, new findings, more research needed fully comprehend biological function disease relevance, especially neurobiology.

Language: Английский

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Decoding the general role of tRNA queuosine modification in eukaryotes

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Transfer RNA (tRNA) contains modified nucleosides essential for modulating protein translation. One of these modifications is queuosine (Q), which affects NAU codons translation rate. For decades, multiple studies have reported a wide variety species-specific Q-related phenotypes in different eukaryotes, hindering the identification general underlying mechanism behind that phenotypic diversity. Here, through bioinformatics analysis representative eukaryotic genomes we predicted: i) genes enriched codons, whose would be affected by tRNA Q-modification (Q-genes); and ii) specific biological processes each organism Q-genes, generally eukaryotes related to ubiquitination, phosphatidylinositol metabolism, splicing, DNA repair or cell cycle. These results provide evidence support first time diversity associated with previously described various species directly depend on control Q-genes translation, allow prediction unknown Q-dependent processes, such as Akt activation p53 expression, tested human cancer cells. Considering relevance our findings may further exploration role Q other pathologies. Moreover, since must salvage from bacteria, suggest changes supply microbiome affect expression host altering its physiology.

Language: Английский

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Deciphering the Diversity of Bacterial Transporters that Salvage Queuosine Precursors

Published: March 5, 2024

Queuosine (Q) is a modification of the wobble base tRNA harboring GUN antico-dons with roles in decoding accuracy and efficiency. Its synthesis complex mul-tiple enzymatic steps several pathway intermediates can be salvaged. The only two transporter families known to salvage Q precursors are QPTR/COG1738 QrtT/QueT. Analysis distribution genes human gut oral microbiota genomes have suggested that more fami-lies remained found precursor exchanges must occur within struc-tured microenvironments mammalian host. Using physical clustering fu-sion-based association genes, candidate for missing transporters were identified five tested experimentally by complementation assays Escherichia coli. Three encoding from three different Pfam families, Ureide permease (PF07168) Acidobacteriota bacterium, Hemolysin III family pro-tein (PF03006) Bifidobacterium breve, Major Facilitator Superfamily protein (PF07690) Bartonella henselae, allow transport both preQ0 preQ1 this heterologous system. This work suggests many evolve reinforcing concept plasticity.

Language: Английский

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tRNA modifications inform tissue specific mRNA translation and codon optimization

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 26, 2023

Abstract The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role fine-tuning codon decoding at tissue or cell levels remains incomplete. Here, we analyzed seven tissues from mice for expression modifications and mature tRNAs well decoding. analysis revealed distinct enrichment patterns tissues. Queuosine (Q) modification was most enriched brain compared to other tissues, while mitochondrial highest heart. Using three different metrics analysis; isoacceptors frequencies, total A-site pausing, a strong bias towards A/T ending codons except brain. this observation, synthesized, delivered vivo , mutated EGFP Q-codons, where C-ending Q-codons were replaced with U-ending codons. protein mutant downregulated liver, which is poor Q, when NAC exchanged NAU codons, did not change. This data shows that understanding enrichments across only essential bias, but it can also be utilized optimizing gene therapeutics more tissue, cell, condition specific.

Language: Английский

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