Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments
Chen, J.; Mo, Z.; Chen, S.; Liu, K. F.; Li, Q.; Greenberg, R. A.; Hsu, T. Y.-T.; Torres, C.; Wang, X.; Hur, S.
Show abstract
ADAR1 converts adenosine to inosine in endogenous double-stranded RNAs (dsRNAs) to prevent excessive MDA5-driven interferon-stimulated gene expression. The source of endogenous immunogenic dsRNAs remains enigmatic because only a small fraction of ADAR1 substrates activate MDA5, and cellular MDA5 filaments have not been isolated. Here, we couple affinity purification of cellular MDA5 filaments with RNA sequencing to define immunogenic endogenous dsRNAs. Greater than 84% of dsRNAs suppressed by combined DDX3X RNA helicase and ADAR1 base-editing activities were present in MDA5 filaments, compared to less than 1% of dsRNA substrates acted on by ADAR1 alone. Dual substrate dsRNAs consisted of inverted repeats embedded in 3-UTRs with high base-pair complementarity and longer intervening sequences between repeats, with a minor contribution coming from intermolecular dsRNAs formed by sense and antisense transcripts. Moreover, the majority of dual substrate immunogenic dsRNAs were hyperedited in DDX3X mutant cancers. This reveals the identity of endogenous immunogenic dsRNAs and quality control mechanisms underlying their suppression.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination deficient cells 98%
- BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2 97%
- Polycomb sustains promoters in a deep OFF-state by limiting PIC formation to counteract transcription 97%
Similar papers in this journal
- TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling 98%
- Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein 97%
- Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination 97%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.