RRC ID 65209
Author Mao K, Breen P, Ruvkun G.
Title Mitochondrial dysfunction induces RNA interference in C. elegans through a pathway homologous to the mammalian RIG-I antiviral response.
Journal PLoS Biol
Abstract RNA interference (RNAi) is an antiviral pathway common to many eukaryotes that detects and cleaves foreign nucleic acids. In mammals, mitochondrially localized proteins such as mitochondrial antiviral signaling (MAVS), retinoic acid-inducible gene I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5) mediate antiviral responses. Here, we report that mitochondrial dysfunction in Caenorhabditis elegans activates RNAi-directed silencing via induction of a pathway homologous to the mammalian RIG-I helicase viral response pathway. The induction of RNAi also requires the conserved RNA decapping enzyme EOL-1/DXO. The transcriptional induction of eol-1 requires DRH-1 as well as the mitochondrial unfolded protein response (UPRmt). Upon mitochondrial dysfunction, EOL-1 is concentrated into foci that depend on the transcription of mitochondrial RNAs that may form double-stranded RNA (dsRNA), as has been observed in mammalian antiviral responses. Enhanced RNAi triggered by mitochondrial dysfunction is necessary for the increase in longevity that is induced by mitochondrial dysfunction.
Volume 18(12)
Pages e3000996
Published 2020-12-1
DOI 10.1371/journal.pbio.3000996
PMID 33264285
PMC PMC7735679
MeSH Adaptor Proteins, Signal Transducing Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / metabolism DEAD Box Protein 58 / metabolism* DEAD Box Protein 58 / physiology DEAD-box RNA Helicases / metabolism Gene Expression Regulation / genetics Interferon-Induced Helicase, IFIH1 / metabolism Mitochondria / metabolism* Mitochondria / physiology RNA Interference / physiology* RNA, Double-Stranded / genetics RNA, Small Interfering / genetics RNA, Viral / genetics Signal Transduction / genetics
C.elegans tm1329