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NMD is essential fo...
NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements
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Weischenfeldt, Joachim (author)
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Damgaard, Inge (author)
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- Bryder, David (author)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups
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Theilgaard-Moench, Kim (author)
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- Thorén, Lina (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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Nielsen, Finn Cilius (author)
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- Jacobsen, Sten Eirik W (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Nerlov, Claus (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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Porse, Bo Torben (author)
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(creator_code:org_t)
- 2008-05-15
- 2008
- English.
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In: Genes & Development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 22:10, s. 1381-1396
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http://dx.doi.org/10... (free)
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http://genesdev.cshl...
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Abstract
Subject headings
Close
- Nonsense-mediated mRNA decay (NMD) is a post-transcriptional surveillance process that eliminates mRNAs containing premature termination codons (PTCs). NMD has been hypothesized to impact on several aspects of cellular function; however, its importance in the context of a mammalian organism has not been addressed in detail. Here we use mouse genetics to demonstrate that hematopoietic-specific deletion of Upf2, a core NMD factor, led to the rapid, complete, and lasting cell-autonomous extinction of all hematopoietic stem and progenitor populations. In contrast, more differentiated cells were only mildly affected in Upf2-null mice, suggesting that NMD is mainly essential for proliferating cells. Furthermore, we show that UPF2 loss resulted in the accumulation of nonproductive rearrangement by-products from the Tcrb locus and that this, as opposed to the general loss of NMD, was particularly detrimental to developing T-cells. At the molecular level, gene expression analysis showed that Upf2 deletion led to a profound skewing toward up-regulated mRNAs, highly enriched in transcripts derived from processed pseudogenes, and that NMD impacts on regulated alternative splicing events. Collectively, our data demonstrate a unique requirement of NMD for organismal survival.
Subject headings
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Keyword
- alternative splicing
- programmed DNA rearrangements
- T-cell development
- nonsense-mediated mRNA decay
- hematopoietic stem and progenitor cells
- pseudogenes
Publication and Content Type
- art (subject category)
- ref (subject category)
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