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ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through editing-dependent and -independent mechanisms - PubMed

3 days ago
  • #dsRNA
  • #mitochondria
  • #ADAR1
  • ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through both editing-dependent and -independent mechanisms.
  • ADAR1 suppresses aberrant immune activation by self-dsRNAs, but its influence on the cellular dsRNA landscape was unclear.
  • Quantitative dsRNA sequencing reveals dsRNAs are enriched in protein-coding mRNAs with repetitive elements and elongated 3' UTRs, as well as mitochondrial RNAs.
  • ADAR1-regulated dsRNA transcripts include nuclear-encoded mRNAs and mitochondria-encoded RNAs, the latter rarely edited by ADAR1.
  • dsRNAs accumulate to high levels within mitochondria of ADAR1-deficient cells, and ADAR1p150 is detected in mitochondrial fractions.
  • ADAR1 loss sensitizes cells to inflammation under mitochondrial stress (e.g., herniation, X-ray irradiation).
  • ADAR1 controls mitochondrial dsRNAs beyond just A-to-I edited transcripts.