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Related Concept Videos

Transfer RNA Synthesis02:36

Transfer RNA Synthesis

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One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
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Translation01:31

Translation

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Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
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tRNA Activation02:26

tRNA Activation

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Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
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RNA Editing02:23

RNA Editing

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Improving Translational Accuracy02:07

Improving Translational Accuracy

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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Leaky Scanning02:28

Leaky Scanning

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Related Experiment Video

Updated: May 31, 2025

An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity
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An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity

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

Daisuke Ando1,2, Sherif Rashad2,3, Thomas J Begley4

  • 1Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.

International Journal of Molecular Sciences
|January 25, 2025
PubMed
Summary
This summary is machine-generated.

The tRNA epitranscriptome regulates translation. Tissue-specific tRNA modifications, like Queuosine (Q) in the brain, influence gene expression, enabling targeted mRNA therapeutics.

Keywords:
codon optimalitycodon optimizationmRNA translationqueuosineribosome profilingtRNA modifications

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Last Updated: May 31, 2025

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The tRNA epitranscriptome plays a crucial role in regulating mRNA translation.
  • Understanding tissue-specific tRNA expression and modifications is vital for deciphering codon decoding.
  • Current knowledge on the tRNA epitranscriptome's role in fine-tuning translation at the tissue level is incomplete.

Purpose of the Study:

  • To analyze tRNA expression, modifications, and codon optimality across seven mouse tissues.
  • To investigate the tissue-specific enrichment patterns of tRNA modifications.
  • To explore the potential of tRNA modification knowledge for optimizing gene and mRNA therapeutics.

Main Methods:

  • Analysis of tRNA expression and modifications in seven mouse tissues.
  • Assessment of codon optimality.
  • In vivo synthesis and delivery of codon-mutated EGFP (Enhanced Green Fluorescent Protein) to test the impact of Queuosine (Q) codon mutations.

Main Results:

  • Distinct tissue-specific patterns of tRNA modifications were observed.
  • Queuosine (Q) tRNA modification was most enriched in the brain.
  • Mitochondrial tRNA modifications and tRNA expression were highest in the heart.
  • Mutant EGFP protein levels were downregulated in the liver (low Q) but unchanged in the brain (high Q).

Conclusions:

  • Tissue-specific tRNA modification enrichments are essential for understanding codon decoding and bias.
  • Knowledge of tRNA modifications can be leveraged to develop tissue- or cell-specific gene and mRNA therapeutics.
  • This study provides a foundation for engineering targeted gene therapies based on epitranscriptomic profiles.