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ADAR1 is essential for intestinal homeostasis and stem cell maintenance.

Cell death & disease | 2013

Adenosine deaminase acting on RNA 1 (ADAR1) is a double-stranded RNA-editing enzyme that converts adenosine (A) to inosine (I), and essential for normal development. In this study, we reported an essential role of ADAR1 in the survival and maintenance of intestinal stem cells and intestinal homoeostasis by suppressing endoplasmic reticulum (ER) stress and interferon (IFN) signaling. ADAR1 was highly expressed in the Lgr5+ cells, and its deletion in adult mice led to a rapid apoptosis and loss of these actively cycling stem cells in the small intestine and colon. ADAR1 deletion resulted in a drastic expansion of progenitors and Paneth cells but a reduction of three other major epithelial lineages. Moreover, loss of ADAR1 induced ER stress and activation of IFN signaling, and altered expression in WNT targets, followed by intestinal inflammation. An ER stress inhibitor partially suppressed crypt apoptosis. Finally, data from cultured intestinal crypts demonstrated that loss of ADAR1 in the epithelial cells is the primary cause of these effects. These results support an essential role of ADAR1 and RNA editing in tissue homeostasis and stem cells.

Pubmed ID: 23598411 RIS Download

Research resources used in this publication

None found

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: CA121105
  • Agency: NIDDK NIH HHS, United States
    Id: UO1-DK085570
  • Agency: NCI NIH HHS, United States
    Id: P30 CA047904
  • Agency: NCI NIH HHS, United States
    Id: R01 CA121105
  • Agency: NCI NIH HHS, United States
    Id: CA129829
  • Agency: NCI NIH HHS, United States
    Id: R01 CA172136
  • Agency: NIDDK NIH HHS, United States
    Id: U01 DK085532
  • Agency: NIAID NIH HHS, United States
    Id: R21AI078094
  • Agency: NIDDK NIH HHS, United States
    Id: U01 DK085570
  • Agency: NCI NIH HHS, United States
    Id: R01 CA129829
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI078094
  • Agency: NCI NIH HHS, United States
    Id: P30CA047904
  • Agency: NIDDK NIH HHS, United States
    Id: U24 DK085532
  • Agency: NCI NIH HHS, United States
    Id: CA106348
  • Agency: NCI NIH HHS, United States
    Id: R01 CA106348

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