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21.02.19 Miska lab find sex differences in gene silencing by environmental RNA

last modified Feb 28, 2019 10:15 PM
Using C elegans as a model, the Miska lab and colleagues show clear differences between sexes in small RNA abundance that are associated with trans-generational inheritance
21.02.19 Miska lab find sex differences in gene silencing by environmental RNA

Small RNA expression varies between the sexes in C elegans

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

Bezler et al. (2019) PLoS Genet 15(2): e1007905.

DOI: 10.1371/journal.pgen.1007905.


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.


Author summary

Environmental factors such as heat or pathogens influence living organisms, and in some cases these experiences can be passed on to the next generation. One such environmental factor is double stranded RNA that can be taken up by some animals and induce changes in gene expression via small RNA mediated silencing.

Here, we use the roundworm Caenorhabditis elegans to show that the female and male germline react differently to the presence of such an environmental factor that may affect transmission to following generations. Sequencing of gonadal small RNA suggests that the underlying sex-differences affect downstream processing but not uptake.

Furthermore, we describe the naturally occurring small RNA populations of female and male gonads and use genetic mutants to assign small RNAs to the two tissues of the gonad, namely the somatic gonad or the germline. These sex-and tissue-specific small RNA expression data provide an important resource for future research. In addition, this work reveals mechanistic insights into sex-differences in response to environmental cues.



Read more about research in the Miska lab.

Watch Eric Miska describe his research on video.

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The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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