Stalled translation on transcripts cleaved by RNase L activates signaling important for innate immunity

RNase L activation results in detectable amounts of mRNA fragments that are translated. Ribosomes stall at the end of the cleaved mRNA fragments and can be rescued by PELO (top pathway). They also induce activation of ZAKα and the downstream RSR that is known to lead to an inflammatory response and cell death via JNK and p38 (bottom pathway). When PELO is depleted or not expressed, ribosomes are not efficiently rescued. This leads to an accumulation of stalled ribosomes and therefore more persistent activation of the RSR. In this way, PELO serves to tune activation of the RSR.