Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/891
Título: Unspliced Precursors of NMD-Sensitive β-Globin Transcripts Exhibit Decreased Steady-State Levels in Erythroid Cells
Autor: Morgado, Ana
Almeida, Fátima
Silva, Ana Luísa
Romão, Luísa
Palavras-chave: Doenças Genéticas
Genómica Funcional e Estrutural
Data: 4-Jun-2012
Editora: Public Library of Science
Citação: PLoS One. 2012;7(6):e38505. Epub 2012 Jun 4
Resumo: Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and rapidly degrades mRNAs carrying premature translation-termination codons (PTCs). Mammalian NMD depends on both splicing and translation, and requires recognition of the premature stop codon by the cytoplasmic ribosomes. Surprisingly, some published data have suggested that nonsense codons may also affect the nuclear metabolism of the nonsense-mutated transcripts. To determine if nonsense codons could influence nuclear events, we have directly assessed the steady-state levels of the unspliced transcripts of wild-type and PTC-containing human β-globin genes stably transfected in mouse erythroleukemia (MEL) cells, after erythroid differentiation induction, or in HeLa cells. Our analyses by ribonuclease protection assays and reverse transcription-coupled quantitative PCR show that β-globin pre-mRNAs carrying NMD-competent PTCs, but not those containing a NMD-resistant PTC, exhibit a significant decrease in their steady-state levels relatively to the wild-type or to a missense-mutated β-globin pre-mRNA. On the contrary, in HeLa cells, human β-globin pre-mRNAs carrying NMD-competent PTCs accumulate at normal levels. Functional analyses of these pre-mRNAs in MEL cells demonstrate that their low steady-state levels do not reflect significantly lower pre-mRNA stabilities when compared to the normal control. Furthermore, our results also provide evidence that the relative splicing efficiencies of intron 1 and 2 are unaffected. This set of data highlights potential nuclear pathways that might be promoter- and/or cell line-specific, which recognize the NMD-sensitive transcripts as abnormal. These specialized nuclear pathway(s) may be superimposed on the general NMD mechanism.
Peer review: yes
URI: http://hdl.handle.net/10400.18/891
ISSN: 1932-6203
Versão do Editor: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0038505
Aparece nas colecções:DGH - Artigos em revistas internacionais

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