Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Sertoli Cell Number Correlates with Serum Inhibin B in Infant Cryptorchid Boys

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Surgical Management of Undescended Testis - Timetable and Outcome: A Debate

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Shared heritability and functional enrichment across six solid cancers

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Mutant CEBPA directly drives the expression of the targetable tumor-promoting factor CD73 in AML

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Identification of two distinct pathways of human myelopoiesis

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
JournalGenes and Development
Volume22
Issue number10
Pages (from-to)1381-1396
Number of pages16
ISSN0890-9369
DOIs
Publication statusPublished - 15 May 2008

    Research areas

  • Alternative splicing, Hematopoietic stem and progenitor cells, Nonsense-mediated mRNA decay, Programmed DNA rearrangements, Pseudogenes, T-cell development

ID: 55088090