Translational read-through drugs (TRIDs) are able to restore protein expression and ciliogenesis in fibroblasts of patients with retinitis pigmentosa caused by a premature termination codon in FAM161A

dc.contributor.authorBeryozkin, Avigail
dc.contributor.authorSamanta, Ananya
dc.contributor.authorGopalakrishnan, Prakadeeswari
dc.contributor.authorKhateb, Samer
dc.contributor.authorBanin, Eyal
dc.contributor.authorSharon, Dror
dc.contributor.authorNagel-Wolfrum, Kerstin
dc.date.accessioned2023-03-30T13:45:39Z
dc.date.available2023-03-30T13:45:39Z
dc.date.issued2022
dc.description.abstractAtaluren and Gentamicin are translational readthrough drugs (TRIDs) that induce premature termination codon (PTC) readthrough, resulting in the production of full-length proteins that usually harbor a single missense substitution. FAM161A is a ciliary protein which is expressed in photoreceptors, and pathogenic variants in this gene cause retinitis pigmentosa (RP). Applying TRIDs on fibroblasts from RP patients due to PTC in the FAM161A (p.Arg523*) gene may uncover whether TRIDs can restore expression, localization and function of this protein. Fibroblasts from six patients and five age-matched controls were starved prior to treatment with ataluren or gentamicin, and later FAM161A expression, ciliogenesis and cilia length were analyzed. In contrast to control cells, fibroblasts of patients did not express the FAM161A protein, showed a lower percentage of ciliated cells and grew shorter cilia after starvation. Ataluren and Gentamicin treatment were able to restore FAM161A expression, localization and co-localization with α-tubulin. Ciliogenesis and cilia length were restored following Ataluren treatment almost up to a level which was observed in control cells. Gentamicin was less efficient in ciliogenesis compared to Ataluren. Our results provide a proof-of-concept that PTCs in FAM161A can be effectively suppressed by Ataluren or Gentamicin, resulting in a full-length functional protein.en_GB
dc.identifier.doihttp://doi.org/10.25358/openscience-8831
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/8847
dc.language.isoengde
dc.rightsCC-BY-4.0*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc570 Biowissenschaftende_DE
dc.subject.ddc570 Life sciencesen_GB
dc.titleTranslational read-through drugs (TRIDs) are able to restore protein expression and ciliogenesis in fibroblasts of patients with retinitis pigmentosa caused by a premature termination codon in FAM161Aen_GB
dc.typeZeitschriftenaufsatzde
jgu.journal.titleInternational Journal of Molecular Sciencesde
jgu.journal.volume23de
jgu.organisation.departmentFB 10 Biologiede
jgu.organisation.nameJohannes Gutenberg-Universität Mainz
jgu.organisation.number7970
jgu.organisation.placeMainz
jgu.organisation.rorhttps://ror.org/023b0x485
jgu.pages.alternative3541de
jgu.publisher.doi10.3390/ijms23073541de
jgu.publisher.issn1422-0067de
jgu.publisher.nameMDPIde
jgu.publisher.placeLausannede
jgu.publisher.year2022
jgu.rights.accessrightsopenAccess
jgu.subject.ddccode570de
jgu.subject.dfgNaturwissenschaftende
jgu.type.contenttypeScientific articlede
jgu.type.dinitypeArticleen_GB
jgu.type.resourceTextde
jgu.type.versionPublished versionde

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