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Transfer RNA Synthesis02:36

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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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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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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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Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
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Viral Codon Usage and the Host Transfer RNA.

Elena Muscolino1, Juana Díez1

  • 1Molecular Virology Group, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain;

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|April 23, 2025
PubMed
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Viruses like chikungunya virus (CHIKV) use host transfer RNA (tRNA) modifications to overcome challenges with suboptimal codons, enhancing viral protein production during infection. This strategy may offer new antiviral therapy targets.

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DNA damage responsecodon optimalitycodon usagemcm5/mcm5s2tRNA epitranscriptomeviruses

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Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Efficient viral protein production is crucial for viral replication within host cells.
  • Many viral genomes contain suboptimal codons, which paradoxically can limit protein output.
  • Host transfer RNA (tRNA) modifications, forming the tRNA epitranscriptome, are increasingly recognized as key regulators of translation.

Purpose of the Study:

  • To investigate how viruses, using chikungunya virus (CHIKV) as a model, manage translation despite suboptimal codon usage.
  • To explore the role of the host tRNA epitranscriptome in viral replication.
  • To identify potential therapeutic targets for broad-spectrum antiviral strategies.

Main Methods:

  • Analysis of viral genome sequences for codon usage patterns.
  • Investigating the impact of CHIKV infection on host cell stress responses.
  • Characterizing changes in the tRNA epitranscriptome following CHIKV infection.
  • Assessing the selective translation of suboptimal codons in infected cells.

Main Results:

  • CHIKV infection induces a DNA damage stress response, altering the host tRNA epitranscriptome.
  • These tRNA modifications reprogram codon optimality, favoring the translation of specific suboptimal codons.
  • These targeted codons are prevalent in both CHIKV's genome and host stress response genes.
  • Viral codon usage is optimized to the modified tRNA landscape in infected cells.

Conclusions:

  • The interplay between viral codon usage, host stress responses, and tRNA modifications is a conserved viral strategy.
  • This mechanism allows viruses to efficiently produce proteins despite suboptimal codon usage.
  • Targeting this virus-host interaction presents a promising avenue for developing novel antiviral therapies.