TY - JOUR
T1 - Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment
AU - Bezler, Alexandra
AU - Braukmann, Fabian
AU - West, Sean M.
AU - Duplan, Arthur
AU - Conconi, Raffaella
AU - Schütz, Frédéric
AU - Gönczy, Pierre
AU - Piano, Fabio
AU - Gunsalus, Kristin
AU - Miska, Eric A.
AU - Keller, Laurent
N1 - Funding Information:
This work was funded by grants from the Swiss National Science Foundation and an advanced European Research Council grant to LK, grants from Cancer Research UK (C13474/A18583, C6946/A14492) and the Wellcome Trust (104640/Z/14/Z, 092096/Z/10/Z) to EAM, and grants from the National Institutes of Health to SW (NIGMS NHRA 5F32GM100614) and to FP and KCG (NHGRI U01 HG004276, NICHD R01 HD046236), and by research funding from New York University Abu Dhabi to FP and KCG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to Scott Aoki and Judith Kimble for sharing strains prior to publication, Benita Wolf, Adria LeBoeuf, Tamara Mikeladze-Dvali, Nicolas Bologna, David Jordan and two anonymous reviewers for comments on the manuscript and the Gönczy and Miska lab members for advice. We thank Kay Harnish of the Gurdon Institute Sequencing Facility for managing the high-throughput sequencing, Coralie Busso and Nazife Bega for assistance and Wormbase. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).
Publisher Copyright:
© 2019 Bezler et al. http://creativecommons.org/licenses/by/4.0/.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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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U2 - 10.1371/journal.pgen.1007905
DO - 10.1371/journal.pgen.1007905
M3 - Article
C2 - 30735500
AN - SCOPUS:85061961402
SN - 1553-7390
VL - 15
JO - PLoS genetics
JF - PLoS genetics
IS - 2
M1 - e1007905
ER -