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

Publication type:
Journal article
Metadata:
Abstract
<jats:p>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.</jats:p>
Autoren
  • Avigail Beryozkin
  • Ananya Samanta
  • Prakadeeswari Gopalakrishnan
  • Samer Khateb
  • Eyal Banin
  • Dror Sharon
  • Kerstin Nagel-Wolfrum
DOI
10.3390/ijms23073541
eISSN
1422-0067
Ausgabe der Veröffentlichung
7
Zeitschrift
International Journal of Molecular Sciences
Sprache
en
Online publication date
2022
Paginierung
3541 - 3541
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/ijms23073541
Datum der Datenerfassung
2022
Titel
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
Ausgabe der Zeitschrift
23

Data source: Crossref

Other metadata sources:
Author's licence
CC-BY
Autoren
  • Avigail Beryozkin
  • Ananya Samanta
  • Prakadeeswari Gopalakrishnan
  • Samer Khateb
  • Eyal Banin
  • Dror Sharon
  • Kerstin Nagel-Wolfrum
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-491381577-G
Resource version
Published version
DOI
10.3390/ijms23073541
File(s) embargoed
false
Open access
true
ISSN
1422-0067
Zeitschrift
International Journal of Molecular Sciences
Schlüsselwörter
  • 570 Biowissenschaften
  • 570 Life sciences
Sprache
eng
Open access status
Open Access
Paginierung
3541
Datum der Veröffentlichung
2022
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/8847
Herausgeber
MDPI
Datum der Datenerfassung
2023
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Zugang
Public
Titel
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
Ausgabe der Zeitschrift
23

Files

translational_readthrough_dru-20230221164839296.pdf

Data source: OPENSCIENCE.UB

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