Defects in intron recycling suppress the antiviral response via a mechanism of intronic endogenous dsRNA - PubMed
a day ago
- #dsRNA
- #antiviral response
- #intron recycling
- Defects in intron recycling, specifically due to loss of the lariat debranching enzyme DBR1, lead to cytoplasmic accumulation of intron lariats.
- Intronic inverted repeats Alu (IR Alus) form long double-stranded RNA (dsRNA) structures when lariats escape recycling, which normally degrade after splicing.
- Viral introns evolve to avoid dsRNA, whereas human introns are enriched for them.
- DBR1 deficiency elevates cytoplasmic dsRNA and attenuates RNase L and PKR signaling, potentially explaining viral susceptibility in DBR1-deficient cells.
- Cytoplasmic RIP-seq shows introns are a more abundant source of IR Alus than 3' UTRs in WT cells.
- The high load of IR Alus in introns makes lariat recycling efficiency a key modulator of endogenous dsRNA levels in human cells.