RNA 5-methylcytosine marks mitochondrial double-stranded RNAs for degradation and cytosolic release.

ABSTRACT: Mitochondria are essential regulators of innate immunity. They generate long mitochondrial double-stranded RNAs (mt-dsRNAs) and release them into the cytosol to trigger an immune response under pathological stress conditions. Yet the regulation of these self-immunogenic RNAs remains largely unknown. Here, we employ CRISPR screening on mitochondrial RNA (mtRNA)-binding proteins and identify NOP2/Sun RNA methyltransferase 4 (NSUN4) as a key regulator of mt-dsRNA expression in human cells. We find that NSUN4 induces 5-methylcytosine (m⁵C) modification on mtRNAs, especially on the termini of light-strand long noncoding RNAs. These m⁵C-modified RNAs are recognized by complement C1q-binding protein (C1QBP), which recruits polyribonucleotide nucleotidyltransferase to facilit

SUBMITTER: Kim S 

PROVIDER: S-EPMC11316625 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature