Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Shared heritability and functional enrichment across six solid cancers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Regulation of ETAA1-mediated ATR activation couples DNA replication fidelity and genome stability

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Publisher Correction: Shared heritability and functional enrichment across six solid cancers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftGenes and Development
Vol/bind22
Udgave nummer10
Sider (fra-til)1381-1396
Antal sider16
ISSN0890-9369
DOI
StatusUdgivet - 15 maj 2008

ID: 55088090