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Related Concept Videos

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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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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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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 flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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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.
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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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Codon optimality has minimal effect on determining translation efficiency in mycobacterium tuberculosis.

Smitha Soman1, Somdeb Chattopadhyay2, Siya Ram1,3

  • 1School of Biotechnology, Gautam Buddha University, Gautam Budh Nagar, Greater Noida, Uttar Pradesh, India.

Scientific Reports
|January 9, 2023
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Summary

Mycobacterium tuberculosis (Mtb) translation efficiency is optimized by co-evolution of its tRNA pool and codon usage. Despite single tRNA copies, varying tRNA levels ensure abundant tRNAs decode frequently used codons, minimizing negative impacts.

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Area of Science:

  • Microbiology
  • Genomics
  • Molecular Biology

Background:

  • Mycobacterium tuberculosis (Mtb) possesses a high GC-content genome, leading to significant codon usage biases.
  • Codon usage impacts mRNA translation accuracy, efficiency, and protein folding.

Purpose of the Study:

  • To investigate the role of codon usage bias in determining mRNA translation efficiency in Mtb.
  • To analyze the relationship between tRNA levels, codon adaptability, and translation efficiency in Mtb.

Main Methods:

  • Analysis of Mtb's unique tRNA gene copy number and relative tRNA pool levels.
  • Correlation analysis between genomic codon usage, tRNA adaptability (TAc), and mRNA abundance.
  • Estimation of codon and mRNA optimality using TAc and tRNA demand.

Main Results:

  • Mtb exhibits significant variation in tRNA pool levels, with abundant tRNAs decoding preferred codons.
  • A positive correlation exists between genomic codon usage and tRNA adaptability (TAc).
  • Neither TAc nor tRNA demand correlated with mRNA abundance, translation efficiency, or ribosome pausing.

Conclusions:

  • The translation machinery and tRNA pool in Mtb co-evolve to optimize translation efficiency.
  • Maladaptive codon effects are minimized due to this co-evolutionary process.