Deficiency of m6A RNA methylation promotes ZBP1 mediated cell death

Deficiency of m6A provokes inflammatory responses and cell death, but the underlying mechanisms remain elusive. Here we showed that the noncoding RNA 7SK gains the immunostimulatory potential upon m6A depletion and subsequently activates RIG-I/MAVS axis to spark interferon (IFN) signaling cascades.

Concomitant excess of IFN and m6A deficiency synergistically facilitate the formation of RNA G-quadruplexes (rG4) to promote ZBP1-mediated necroptotic cell death.