Article

The efficiency of nonsense-mediated mRNA decay is an inherent character and varies among different cells

Department of Genetics, Life Sciences Institute, The Hebrew University, Jerusalem, Israel.
European Journal of HumanGenetics (Impact Factor: 4.35). 12/2007; 15(11):1156-62. DOI: 10.1038/sj.ejhg.5201889
Source: PubMed

ABSTRACT

Nonsense-mediated mRNA decay (NMD) is a mechanism, which selectively degrades transcripts carrying premature termination codons (PTCs) and a variety of physiologic transcripts containing NMD-inducing features. In a recent study, we have found variable NMD efficiency among nasal epithelial cells obtained from cystic fibrosis (CF) patients. This variability was found for CF transmembrane conductance regulator (CFTR) transcripts carrying the W1282X PTC, as well as for several NMD physiologic substrates. Here, we aimed to investigate the possibility that variability in NMD efficiency is a more generalized phenomenon and is not restricted to nasal epithelial cells. To investigate this possibility, we analyzed the NMD efficiency of both a CFTR constructs carrying the W1282X PTC and beta-globin constructs carrying the NS39 PTC, in HeLa and MCF7 cells. Variability in NMD efficiency was found for both constructs between the cells, such that in HeLa cells the NMD was highly efficient and in MCF7 the efficiency was significantly lower. Moreover, similar differences in the efficiency of NMD were found for five endogenous NMD physiologic transcripts. Altogether, our results demonstrate existence of cells in which NMD of all transcripts is efficient, whereas others in which the NMD is less efficient, suggesting that the efficiency of NMD is an inherent character of cells. Our results also suggest that variability in the efficiency of NMD is a general phenomenon and is not restricted to nasal epithelial cells. As NMD affects the level of many transcripts, variability in the NMD efficiency might play a role as a genetic modifier of different cellular functions.

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Available from: Gabriele Neu-Yilik, Jun 26, 2014
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    • "Class V: mutations that reduce CFTR protein levels, often by affecting splicing and generating both aberrant mRNA transcripts and a reduced amount of normal mRNA transcripts[4,5]. With this type of mutation it is sometimes challenging to establish their effect on the overall CFTR function and therefore their involvement in the disease, which has a direct and significant impact on genetic counseling[7]. Class VI: mutations that include those that decrease the retention and stability of CFTR at the cell surface. "
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    Full-text · Article · Sep 2015 · FEBS Journal
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    • "Beside the common F508del variant, our CF patients carry missense and nonsense alterations in the CFTR gene. Indeed, different studies have shown that the effect of nonsense mutations on CFTR mRNA levels are very variable [16] and nonsense-mediated decay (NMD) is addressed as the major mechanism for rapid degradation of aberrant transcripts harboring premature termination codons. Interestingly, microRNAs have recently been defined as important regulators of the NMD efficiency [17]. "
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    Full-text · Article · Apr 2013 · Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society
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    • "Since NMD efficiency is known to vary among target transcripts and cell types and NMD machinery does not reduce the level of PTC-containing mRNA to 0% (23,47-54), a small fraction of PTC-containing mRNAs would be resistant to NMD and remain in the cytoplasm. For instance, many reports showed that the abundance of β-globin mRNAs harboring a PTC is reduced to 5-30% of normal level (27,28,34,52,55-61). The remaining NMD-resistant mRNAs, despite being targeted for NMD, would still have EJCs downstream of PTC. "
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