Intergenerational Pathogen-Induced Diapause in Caenorhabditis elegans Is Modulated by mir-243

Abstract

The interaction and communication between bacteria and their hosts modulate many aspects of animal physiology and behavior. Dauer entry as a response to chronic exposure to pathogenic bacteria in Caenorhabditis elegans is an example of a dramatic survival response. This response is dependent on the RNA interference (RNAi) machinery, suggesting the involvement of small RNAs (sRNAs) as effectors. Interestingly, dauer formation occurs after two generations of interaction with two unrelated moderately pathogenic bacteria. Therefore, we sought to discover the identity of C. elegans RNAs involved in pathogen-induced diapause. Using transcriptomics and differential expression analysis of coding and long and small noncoding RNAs, we found that mir-243-3p (the mature form of mir-243) is the only transcript continuously upregulated in animals exposed to both Pseudomonas aeruginosa and Salmonella enterica for two generations. Phenotypic analysis of mutants showed that mir-243 is required for dauer formation under pathogenesis but not under starvation. Moreover, DAF-16, a master regulator of defensive responses in the animal and required for dauer formation was found to be necessary for mir-243 expression. This work highlights the role of a small noncoding RNA in the intergenerational defensive response against pathogenic bacteria and interkingdom communication.

The interaction and communication between bacteria and their hosts modulate many aspects of animal physiology and behavior. Dauer entry as a response to chronic exposure to pathogenic bacteria in Caenorhabditis elegans is an example of a dramatic survival response. This response is dependent on the RNA interference (RNAi) machinery, suggesting the involvement of small RNAs (sRNAs) as effectors. Interestingly, dauer formation occurs after two generations of interaction with two unrelated moderately pathogenic bacteria. Therefore, we sought to discover the identity of C. elegans RNAs involved in pathogen-induced diapause. Using transcriptomics and differential expression analysis of coding and long and small noncoding RNAs, we found that mir-243-3p (the mature form of mir-243) is the only transcript continuously upregulated in animals exposed to both Pseudomonas aeruginosa and Salmonella enterica for two generations. Phenotypic analysis of mutants showed that mir-243 is required for dauer formation under pathogenesis but not under starvation. Moreover, DAF-16, a master regulator of defensive responses in the animal and required for dauer formation was found to be necessary for mir-243 expression. This work highlights the role of a small noncoding RNA in the intergenerational defensive response against pathogenic bacteria and interkingdom communication.