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Review

Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)

  • Authors:
    • John Karijolich
    • Yi-Tao Yu
  • View Affiliations / Copyright

    Affiliations: Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA, Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
  • Pages: 355-362
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    Published online on: June 17, 2014
       https://doi.org/10.3892/ijmm.2014.1809
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Abstract

An estimated one-third of genetic disorders are the result of mutations that generate premature termination codons (PTCs) within protein coding genes. These disorders are phenotypically diverse and consist of diseases that affect both young and old individuals. Various small molecules have been identified that are capable of modulating the efficiency of translation termination, including select antibiotics of the aminoglycoside family and multiple novel synthetic molecules, including PTC124. Several of these agents have proved their effectiveness at promoting nonsense suppression in preclinical animal models, as well as in clinical trials. In addition, it has recently been shown that box H/ACA RNA-guided peudouridylation, when directed to modify PTCs, can also promote nonsense suppression. In this review, we summarize our current understanding of eukaryotic translation termination and discuss various methods for promoting the read-through of disease-causing PTCs, as well as the current obstacles that stand in the way of using the discussed agents broadly in clinical practice.
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Copy and paste a formatted citation
Spandidos Publications style
Karijolich J and Yu Y: Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review). Int J Mol Med 34: 355-362, 2014.
APA
Karijolich, J., & Yu, Y. (2014). Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review). International Journal of Molecular Medicine, 34, 355-362. https://doi.org/10.3892/ijmm.2014.1809
MLA
Karijolich, J., Yu, Y."Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)". International Journal of Molecular Medicine 34.2 (2014): 355-362.
Chicago
Karijolich, J., Yu, Y."Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)". International Journal of Molecular Medicine 34, no. 2 (2014): 355-362. https://doi.org/10.3892/ijmm.2014.1809
Copy and paste a formatted citation
x
Spandidos Publications style
Karijolich J and Yu Y: Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review). Int J Mol Med 34: 355-362, 2014.
APA
Karijolich, J., & Yu, Y. (2014). Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review). International Journal of Molecular Medicine, 34, 355-362. https://doi.org/10.3892/ijmm.2014.1809
MLA
Karijolich, J., Yu, Y."Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)". International Journal of Molecular Medicine 34.2 (2014): 355-362.
Chicago
Karijolich, J., Yu, Y."Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)". International Journal of Molecular Medicine 34, no. 2 (2014): 355-362. https://doi.org/10.3892/ijmm.2014.1809
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