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Related Concept Videos

Translation01:31

Translation

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Lesson: Translation
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.
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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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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
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The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
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Hepatitis A Virus Codon Usage: Implications for Translation Kinetics and Capsid Folding.

Rosa M Pintó1,2, Francisco-Javier Pérez-Rodríguez1,2, Lucia D'Andrea1,2

  • 1Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, 08028 Barcelona, Spain.

Cold Spring Harbor Perspectives in Medicine
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Summary

Hepatitis A virus (HAV) uses biased codon usage to evade host defenses, avoiding competition for essential transfer RNAs (tRNAs). This strategy impacts viral protein folding and stability, offering insights into virus-host interactions.

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Area of Science:

  • Virology
  • Molecular Biology
  • Genomics

Background:

  • Codon usage bias is a universal genomic phenomenon.
  • Hepatitis A virus (HAV) exhibits significant codon usage bias, deoptimized relative to its host.
  • This deoptimization affects HAV's ability to induce host translational shutoff and limits internal ribosome entry site (IRES) efficiency.

Purpose of the Study:

  • To investigate the strategic implications of Hepatitis A virus (HAV) codon usage bias in its interaction with host cells.
  • To elucidate how HAV's codon usage influences tRNA availability and translation dynamics.
  • To explore the link between codon usage, protein structure modulation, and viral stability.

Main Methods:

  • Comparative analysis of HAV codon usage against host cellular messenger RNA (mRNA) codon frequencies.
  • Examination of the relationship between codon usage patterns and translation elongation rates.
  • Assessment of the impact of rare codons on viral capsid folding and stability.

Main Results:

  • HAV preferentially utilizes intermediate host cell codons while avoiding abundant and rare ones, suggesting a 'hawk-dove' game strategy for tRNA access.
  • The use of rare codons in the capsid coding region slows translation elongation.
  • Slower translation rates intrinsically modulate capsid folding, enhancing viral stability for fecal-oral transmission.

Conclusions:

  • HAV's codon usage deoptimization is a sophisticated strategy to manage host resources and ensure viral propagation.
  • The observed codon usage patterns directly influence viral protein structure and stability.
  • HAV serves as a model for understanding codon usage as a regulatory code influencing protein structure and function.