Authors:	Beryozkin, Avigail Samanta, Ananya Gopalakrishnan, Prakadeeswari Khateb, Samer Banin, Eyal Sharon, Dror Nagel-Wolfrum, Kerstin
Title:	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
Online publication date:	30-Mar-2023
Year of first publication:	2022
Language:	english
Abstract:	Ataluren 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.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8831
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	International Journal of Molecular Sciences 23
Pages or article number:	3541
Publisher:	MDPI
Publisher place:	Lausanne
Issue date:	2022
ISSN:	1422-0067
Publisher DOI:	10.3390/ijms23073541
Appears in collections:	DFG-491381577-G