Open AccessMitochondrial dysfunction induces RNA interference in C. elegans through a pathway homologous to the mammalian RIG-I antiviral response
Author(s) -
Kai Mao,
Peter C. Breen,
Gary Ruvkun
Publication year - 2020
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3000996
Subject(s) - biology , rna interference , microbiology and biotechnology , caenorhabditis elegans , rna silencing , rna , mitochondrion , mda5 , gene silencing , genetics , gene
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 (UPR mt ). 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.