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PLoS Genet. 2019 Feb 8;15(2):e1007905. doi: 10.1371/journal.pgen.1007905. [Epub ahead of print]

Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment.

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Department of Ecology and Evolution, University of Lausanne, Lausanne, Switzerland.
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.
Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom.
Center for Genomics & Systems Biology, New York University, New York, New York, United States of America.
Bioinformatics Core Facility; SIB Swiss Institute of Bioinformatics and Centre for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Center for Genomics & Systems Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.


RNA interference (RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter- and trans-generational inheritance. In the nematode Caenorhabditis elegans, environmental double-stranded RNA provided by feeding can lead to heritable changes in phenotype and gene expression. Notably, transmission efficiency differs between the male and female germline, yet the underlying mechanisms remain elusive. Here we use high-throughput sequencing of dissected gonads to quantify sex-specific endogenous piRNAs, miRNAs and siRNAs in the C. elegans germline and the somatic gonad. We identify genes with exceptionally high levels of secondary 22G RNAs that are associated with low mRNA expression, a signature compatible with silencing. We further demonstrate that contrary to the hermaphrodite germline, the male germline, but not male soma, is resistant to environmental RNAi triggers provided by feeding, in line with previous work. This sex-difference in silencing efficacy is associated with lower levels of gonadal RNAi amplification products. Moreover, this tissue- and sex-specific RNAi resistance is regulated by the germline, since mutant males with a feminized germline are RNAi sensitive. This study provides important sex- and tissue-specific expression data of miRNA, piRNA and siRNA as well as mechanistic insights into sex-differences of gene regulation in response to environmental cues.

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Conflict of interest statement

The authors have declared that no competing interests exist.

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