Researchers identify an essential enzyme needed to keep blood stem cells healthy online in Nature Immunology. Inactivation of this enzyme, called ADAR1, increases production of inflammatory mediators and affects cell survival, leading to premature death. The findings suggest ADAR1 might protect individuals against chronic inflammation and autoimmune diseases.
Stuart Orkin and his team studied mice whose blood systems had been reconstituted with blood stem cells from embryos lacking ADAR1. This enzyme is known to edit 'messages' or RNA that arise from expressed genes. Importantly, ADAR1 only acts on double-stranded regions of RNA molecules where it changes some letters of the genetic alphabet. These 'edited' RNAs may have changed protein coding capacity or altered functions.
Surprisingly, Orkin's group finds blood stem cells require ADAR1, dying prematurely without it. ADAR-1 deficient animals spontaneously express more interferon, an alarm molecule that causes systemic inflammation, which amplifies the demise of blood cell formation. The authors speculate that ADAR1 might sense cryptic virus-like RNAs that have invaded host genomes and protects against the harmful effects of chronic interferon expression.
Stuart Orkin (Dana-Farber Cancer Institute; Harvard Medical School, Boston, MA, USA)
Abstract available online. (C) Nature Immunology press release.
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