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

ABSTRACT: RNase L is an endonuclease that responds to infections by cleaving most host- and pathogen-derived single-stranded RNAs. This widespread RNA cleavage can lead to death of the infected cell via the ribotoxic stress response (RSR). An ongoing challenge is to understand how RNase L's endonuclease activity triggers cell death to benefit the host. To address this question, we used nanopore-based long-read sequencing to show that 3' mRNA fragments in the cell were not fully degraded after RNase L activation and that these fragments were translated by ribosomes. We further asked whether ribosomes on mRNA fragments stall when they reach 3' ends created by RNase L. We used ribosome profiling to capture footprints protected by these ribosomes, which can be identified by their short length (15-18 nt)

SUBMITTER: Karasik A 

PROVIDER: S-EPMC12190479 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature