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

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Bezler, Alexandra 
West, Sean M 
Duplan, Arthur 
Conconi, Raffaella 

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.

Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Female, Gene Expression Regulation, Germ Cells, Gonads, High-Throughput Nucleotide Sequencing, Male, MicroRNAs, RNA Interference, RNA, Double-Stranded, RNA, Messenger, RNA, Small Interfering, Sex Characteristics
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PLoS Genet
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Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (104640/Z/14/Z)
Cancer Research UK (18583)
Cancer Research Uk (None)
This work was funded by grants from the Swiss National Science Foundation and an advanced European Research Council grant to Laurent Keller, grants from Cancer Research UK (C13474/A18583, C6946/A14492) and the Wellcome Trust (104640/ Z/14/Z, 092096/Z/10/Z) to Eric A. Miska, and grants from the National Institutes of Health to Sean M. West (NIGMSNHRA 5F32GM100614) and to Fabio Piano and Kristin Gunsalus (NHGRI U01 HG004276, NICHD R01 HD046236), and by research funding from New York University Abu Dhabi to Fabio Piano and Kristin Gunsalus.