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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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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
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Xenopus laevis as a Model to Identify Translation Impairment
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Diphthamide - a conserved modification of eEF2 with clinical relevance.

Raffael Schaffrath1, Ulrich Brinkmann2

  • 1Institut für Biologie, Fachgebiet Mikrobiologie, Universität Kassel, Kassel, Germany.

Trends in Molecular Medicine
|December 14, 2023
PubMed
Summary

Diphthamide, a crucial translation factor modification, ensures reading-frame accuracy. Its roles extend beyond bacteria to human development, cancer, and viral infections like SARS-CoV-2.

Keywords:
cancerdevelopmentdiphthamide modificationelongation factor 2infectious and rare diseasesmRNA translation

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Diphthamide is a unique post-translational modification of eukaryotic translation elongation factor 2 (eEF2).
  • This modification is essential for maintaining translational fidelity and is conserved across eukaryotes and archaea.
  • Initially known as the target of diphtheria toxin (DT), its significance is now recognized in broader biological contexts.

Purpose of the Study:

  • To review the synthesis, function, and clinical relevance of diphthamide.
  • To explore the association of diphthamide synthesis enzymes with cancer and genetic disorders.
  • To investigate the role of diphthamide in viral restriction, including SARS-CoV-2 and HIV-1.

Main Methods:

  • Literature review of existing research on diphthamide synthesis and function.
  • Analysis of studies linking diphthamide synthesis enzymes (DPH1, DPH3) to cancer and diphthamide deficiency syndrome (DDS).
  • Examination of recent findings on diphthamide's role in viral propagation and host-pathogen interactions.

Main Results:

  • Diphthamide synthesis and function are conserved in eukaryotes and archaea, ensuring translation accuracy.
  • Diphthamide synthesis enzymes are implicated in cancer development and mutations cause diphthamide deficiency syndrome.
  • Diphthamide acts as a restriction factor against viruses like SARS-CoV-2 and HIV-1, which target its synthesis enzymes for degradation.

Conclusions:

  • Diphthamide is a critical factor in translation with implications extending to human health.
  • Understanding diphthamide's roles in cancer and viral infections offers potential therapeutic avenues.
  • Further research into diphthamide biology is crucial for addressing diverse clinical challenges.