title: Nonsense suppression therapies in ocular genetic diseases.
abstract: Premature termination codons (PTCs) are caused by nonsense mutations and this leads to either degradation of the mutant mRNA template by nonsense-mediated decay (NMD) or the production of a non-functional, truncated polypeptide. PTCs contribute significantly to inherited human diseases including ocular disorders. Nonsense suppression therapy allows readthrough of PTCs, thereby rescuing the production of a full-length functional protein. In this review, we highlight the mechanisms that are involved in discriminating normal translation termination from premature termination codons; the current understanding of nonsense-mediated mRNA decay models (NMD); the association and crosstalk between PTC and the underlying dynamic NMD process; and the suppression therapies that have been employed in nonsense-medicated ocular disease models. Defining the mechanistic complexity of PTC and NMD will be important to improve treatments of the numerous genetic disorders caused by PTC mutations.
authors: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, V5Z 3N9, Canada, xw09@mail.ubc.ca.
authors: Xia
authors: X
authors: Wang
authors: Cheryl Y
authors: CY
authors: Gregory-Evans
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use; D018389:Codon, Nonsense / Q000235:genetics*; D015785:Eye Diseases, Hereditary / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008156:Luciferases; D008957:Models, Genetic; D059365:Nonsense Mediated mRNA Decay / Q000187:drug effects / Q000502:physiology*; D010069:Oxadiazoles / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D018389:Codon, Nonsense; D010069:Oxadiazoles; D008156:Luciferases; C515878:ataluren
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