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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2006-11-30
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pubmed:abstractText |
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNAs carrying premature translation termination codons. Generally, NMD is elicited if translation terminates >50-54 nucleotides (nt) upstream of an exon-exon junction. We have previously reported that human beta-globin mRNAs carrying 5'-proximal nonsense mutations (e.g., beta15) accumulate to normal levels, suggesting an exception to the "50-54-nt boundary rule." In the present report, we demonstrate that the strength of the UPF1-dependent NMD of mutant beta-globin mRNAs is specifically determined by the proximity of the nonsense codon to the initiation AUG. This conclusion is supported by a parallel effect of the short ORF size on NMD of nonsense-containing alpha-globin mRNAs. To determine whether the short-ORF effect on NMD response is conserved in heterologous transcripts, we assessed its effects on a set of beta-globin/triosephosphate isomerase (TPI) hybrid mRNAs and on the TPI mRNA. Our data support the conclusion that nonsense mutations resulting in a short ORF are able to circumvent the full activity of the canonical UPF1-dependent NMD pathway.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-10484635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-11023527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-11073965,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-11118221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-11451953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-11532962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-11551508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-12093754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-12228722,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-12446775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-12556474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-12718880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-12730685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-12781131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-14701882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-15040442,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-15161914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-15448691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-15901502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-16285926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-16373489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-16449641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-16452507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-16512835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-16679454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-9049311,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-9628884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-9671053,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17077274-9707591
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Codon, Initiator,
http://linkedlifedata.com/resource/pubmed/chemical/Codon, Nonsense,
http://linkedlifedata.com/resource/pubmed/chemical/Globins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Triose-Phosphate Isomerase,
http://linkedlifedata.com/resource/pubmed/chemical/UPF1 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1355-8382
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2160-70
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17077274-5' Untranslated Regions,
pubmed-meshheading:17077274-Animals,
pubmed-meshheading:17077274-Codon, Initiator,
pubmed-meshheading:17077274-Codon, Nonsense,
pubmed-meshheading:17077274-Globins,
pubmed-meshheading:17077274-Humans,
pubmed-meshheading:17077274-Mice,
pubmed-meshheading:17077274-Open Reading Frames,
pubmed-meshheading:17077274-Protein Biosynthesis,
pubmed-meshheading:17077274-RNA Stability,
pubmed-meshheading:17077274-Recombinant Proteins,
pubmed-meshheading:17077274-Trans-Activators,
pubmed-meshheading:17077274-Transcription, Genetic,
pubmed-meshheading:17077274-Triose-Phosphate Isomerase
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pubmed:year |
2006
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pubmed:articleTitle |
The canonical UPF1-dependent nonsense-mediated mRNA decay is inhibited in transcripts carrying a short open reading frame independent of sequence context.
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pubmed:affiliation |
Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, 1649-016 Lisboa, Portugal.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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