Premature Termination Codon in 5' Region of Desmoplakin and Plakoglobin Genes May Escape Nonsense-Mediated Decay through the Reinitiation of Translation
dc.contributor.author
dc.date.accessioned
2022-03-21T12:52:13Z
dc.date.available
2022-03-21T12:52:13Z
dc.date.issued
2022-01-07
dc.identifier.uri
dc.description.abstract
Arrhythmogenic cardiomyopathy is a heritable heart disease associated with desmosomal mutations, especially premature termination codon (PTC) variants. It is known that PTC triggers the nonsense-mediated decay (NMD) mechanism. It is also accepted that PTC in the last exon escapes NMD; however, the mechanisms involving NMD escaping in 50-PTC, such as reinitiation of translation, are less known. The main objective of the present study is to evaluate the likelihood that desmosomal genes carrying 50-PTC will trigger reinitiation. HL1 cell lines were edited by CRISPR/Cas9 to generate isogenic clones carrying 50-PTC for each of the five desmosomal genes. The genomic context of the ATG in-frame in the 50 region of desmosomal genes was evaluated by in silico predictions. The expression levels of the edited genes were assessed by Western blot and real-time PCR. Our results indicate that the 50-PTC in PKP2, DSG2 and DSC2 acts as a null allele with no expression, whereas in the DSP and JUP gene, N-truncated protein is expressed. In concordance with this, the genomic context of the 50-region of DSP and JUP presents an ATG in-frame with an optimal context for the reinitiation of translation. Thus, 50-PTC triggers NMD in the PKP2, DSG2* and DSC2 genes, whereas it may escape NMD through the reinitiation of the translation in DSP and JUP genes, with no major effects on ACM-related gene expression
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
MDPI (Multidisciplinary Digital Publishing Institute)
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Reproducció digital del document publicat a: https://doi.org/10.3390/ijms23020656
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International Journal of Molecular Sciences, 2022, vol. 23, núm. 2, p. 656
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Articles publicats (D-CM)
dc.rights
Attribution 4.0 International (CC BY 4.0)
dc.rights.uri
dc.source
Vallverdú-Prats, Marta Brugada, Ramon Alcalde Masegu, Mireia 2022 Premature Termination Codon in 5' Region of Desmoplakin and Plakoglobin Genes May Escape Nonsense-Mediated Decay through the Reinitiation of Translation International Journal of Molecular Sciences 23 2 656
dc.subject
dc.title
Premature Termination Codon in 5' Region of Desmoplakin and Plakoglobin Genes May Escape Nonsense-Mediated Decay through the Reinitiation of Translation
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
034707
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
1422-0067