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Cited by 32Retinal Development and DisordersRNA Research and SplicingRNA and protein synthesis mechanisms

CERKL, a Retinal Disease Gene, Encodes an mRNA-Binding Protein That Localizes in Compact and Untranslated mRNPs Associated with Microtubules

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Fathinajafabadi, Alihamze, Pérez-Jiménez, Eva, Riera, Marina, Knecht, Erwin, Gonzàlez-Duarte, Roser·2014·PLoS ONE
DOI 10.1371/journal.pone.0087898PMC PMC3912138
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Abstract

The function of CERKL (CERamide Kinase Like), a causative gene of retinitis pigmentosa and cone-rod dystrophy, still awaits characterization. To approach its cellular role we have investigated the subcellular localization and interaction partners of the full length CERKL isoform, CERKLa of 532 amino acids, in different cell lines, including a photoreceptor-derived cell line. We demonstrate that CERKLa is a main component of compact and untranslated mRNPs and that associates with other RNP complexes such as stress granules, P-bodies and polysomes. CERKLa is a protein that binds through its N-terminus to mRNAs and interacts with other mRNA-binding proteins like eIF3B, PABP, HSP70 and RPS3. Except for eIF3B, these interactions depend on the integrity of mRNAs but not of ribosomes. Interestingly, the C125W CERKLa pathological mutant does not interact with eIF3B and is absent from these complexes. Compact mRNPs containing CERKLa also associate with microtubules and are found in neurites of neural differentiated cells. These localizations had not been reported previously for any member of the retinal disorders gene family and should be considered when investigating the pathogenic mechanisms and therapeutical approaches in these diseases.

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Authors
Fathinajafabadi, A., Pérez-Jiménez, E., Riera, M., Knecht, E., & Gonzàlez-Duarte, R.
Affiliations
  • Centro de Investigacion Principe Felipe (ES)
  • Centre for Biomedical Network Research on Rare Diseases (ES)
Corresponding author
Knecht, Erwin
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-02-03
Volume
9
Issue
2
Pages
e87898
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0087898
PMC
PMC3912138
OpenAlex
W1997734413
Cited by
32
References
39
Citations by year
2026: 1 · 2025: 1 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 2
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (acceptedVersion, other-oa)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Generalitat de Catalunya (2009SGR, 2009SGR-1427)
  • Generalitat Valenciana (PROMETEO/2012/061)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
CERKL, retinitis pigmentosa, cone-rod dystrophy, mRNA-binding proteins, microtubules, stress granules, P-bodies, polysomes, eIF3b, poly(A)-binding protein, HSP70, ribosomal protein S3, photoreceptors, protein-protein interaction, retinal disease genes
MeSH terms
Carrier Proteins, Cells, Cultured, Chromatography, Liquid, Fluorescent Antibody Technique, Humans, Microtubules, Neuroblastoma, Polyribosomes, Retina, Ribonucleoproteins, RNA, Messenger, Tumor Cells, Cultured, Blotting, Western, Alternative Splicing, In Situ Hybridization, Fluorescence, Phosphotransferases (Alcohol Group Acceptor), Microscopy, Confocal, Protein Isoforms, Electrophoretic Mobility Shift Assay, Immunoprecipitation, Tandem Mass Spectrometry

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