Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments - PubMed
5 hours ago
- #ADAR1
- #dsRNA
- #MDA5
- ADAR1 edits adenosine to inosine in endogenous dsRNAs to prevent excessive MDA5-driven interferon responses.
- Cellular MDA5 filaments were isolated via affinity purification and RNA sequencing to identify immunogenic endogenous dsRNAs.
- Over 84% of dsRNAs suppressed by DDX3X helicase and ADAR1 editing were in MDA5 filaments, versus less than 1% from ADAR1 alone.
- Dual substrate dsRNAs include inverted repeats in 3'-UTRs with high complementarity and long intervening sequences, plus some sense-antisense pairs.
- Most immunogenic dsRNAs are hyperedited in DDX3X mutant cancers, revealing their identity and suppression mechanisms.