The Effect of Nonsense Mediated Decay on Transcriptional Activity Within the Novel β-Thalassemia Mutation HBB: c.129delT

Luke Forster, R.M. Ardakani, T. Qadah, Jill Finlayson, Reza Ghassemifar

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    © 2015 Informa Healthcare USA, Inc. All rights reserved. Premature termination codons (PTCs) are caused by mutations in the coding sequences of functional genes resulting in an incorrect assignment of a stop codon. Abnormal and truncated proteins are prevented from being translated due to the rapid degradation of mRNA carrying these mutations by an RNA surveillance mechanism referred to as nonsense mediated decay (NMD). Recently, a novel mutation in a patient from Thailand with the clinical diagnosis of Hb E (HBB: c.79G > A)/β0-thalassemia (Hb E/β0-thal) and whose molecular analysis demonstrated a novel mutation in the β-globin gene, HBB: c.129delT, was reported. The result of this deletion is a frameshift (FSC) resulting in a PTC at codon 60. We have analyzed the impact of this mutation on transcription and translation of the affected β-globin gene using an in vitro model. The quantitative real-time polymerase chain reaction (qReTi-PCR) analysis revealed that this nucleotide mutation resulted in marked mRNA degradation, which we attributed to the NMD mechanism and as such, the expected deleterious truncated HBB was not generated. This result highlights a valuable application of our in vitro gene expression model that can be used to predict possible molecular pathology for any given nucleotide mutations.
    Original languageEnglish
    Pages (from-to)334-339
    JournalHemoglobin
    Volume39
    Issue number5
    DOIs
    Publication statusPublished - 2015

    Fingerprint

    Thalassemia
    Globins
    Genes
    Mutation
    Nucleotides
    Degradation
    Messenger RNA
    Polymerase chain reaction
    Pathology
    Transcription
    Nonsense Codon
    Gene expression
    RNA Stability
    RNA
    Molecular Pathology
    Terminator Codon
    Thailand
    Codon
    Proteins
    Real-Time Polymerase Chain Reaction

    Cite this

    Forster, Luke ; Ardakani, R.M. ; Qadah, T. ; Finlayson, Jill ; Ghassemifar, Reza. / The Effect of Nonsense Mediated Decay on Transcriptional Activity Within the Novel β-Thalassemia Mutation HBB: c.129delT. In: Hemoglobin. 2015 ; Vol. 39, No. 5. pp. 334-339.
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    The Effect of Nonsense Mediated Decay on Transcriptional Activity Within the Novel β-Thalassemia Mutation HBB: c.129delT. / Forster, Luke; Ardakani, R.M.; Qadah, T.; Finlayson, Jill; Ghassemifar, Reza.

    In: Hemoglobin, Vol. 39, No. 5, 2015, p. 334-339.

    Research output: Contribution to journalArticle

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    N2 - © 2015 Informa Healthcare USA, Inc. All rights reserved. Premature termination codons (PTCs) are caused by mutations in the coding sequences of functional genes resulting in an incorrect assignment of a stop codon. Abnormal and truncated proteins are prevented from being translated due to the rapid degradation of mRNA carrying these mutations by an RNA surveillance mechanism referred to as nonsense mediated decay (NMD). Recently, a novel mutation in a patient from Thailand with the clinical diagnosis of Hb E (HBB: c.79G > A)/β0-thalassemia (Hb E/β0-thal) and whose molecular analysis demonstrated a novel mutation in the β-globin gene, HBB: c.129delT, was reported. The result of this deletion is a frameshift (FSC) resulting in a PTC at codon 60. We have analyzed the impact of this mutation on transcription and translation of the affected β-globin gene using an in vitro model. The quantitative real-time polymerase chain reaction (qReTi-PCR) analysis revealed that this nucleotide mutation resulted in marked mRNA degradation, which we attributed to the NMD mechanism and as such, the expected deleterious truncated HBB was not generated. This result highlights a valuable application of our in vitro gene expression model that can be used to predict possible molecular pathology for any given nucleotide mutations.

    AB - © 2015 Informa Healthcare USA, Inc. All rights reserved. Premature termination codons (PTCs) are caused by mutations in the coding sequences of functional genes resulting in an incorrect assignment of a stop codon. Abnormal and truncated proteins are prevented from being translated due to the rapid degradation of mRNA carrying these mutations by an RNA surveillance mechanism referred to as nonsense mediated decay (NMD). Recently, a novel mutation in a patient from Thailand with the clinical diagnosis of Hb E (HBB: c.79G > A)/β0-thalassemia (Hb E/β0-thal) and whose molecular analysis demonstrated a novel mutation in the β-globin gene, HBB: c.129delT, was reported. The result of this deletion is a frameshift (FSC) resulting in a PTC at codon 60. We have analyzed the impact of this mutation on transcription and translation of the affected β-globin gene using an in vitro model. The quantitative real-time polymerase chain reaction (qReTi-PCR) analysis revealed that this nucleotide mutation resulted in marked mRNA degradation, which we attributed to the NMD mechanism and as such, the expected deleterious truncated HBB was not generated. This result highlights a valuable application of our in vitro gene expression model that can be used to predict possible molecular pathology for any given nucleotide mutations.

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