piRNA-guided co-transcriptional silencing coopts nuclear export factors
- University of Cambridge, United Kingdom
Abstract
The PIWI-interacting RNA (piRNA) pathway is a small RNA-based immune system that controls the expression of transposons and maintains genome integrity in animal gonads. In Drosophila, piRNA-guided silencing is achieved, in part, via co-transcriptional repression of transposons by Piwi. This depends on Panoramix (Panx); however, precisely how an RNA binding event silences transcription remains to be determined. Here we show that Nuclear Export Factor 2 (Nxf2) and its co-factor, Nxt1, form a complex with Panx and are required for co-transcriptional silencing of transposons in somatic and germline cells of the ovary. Tethering of Nxf2 or Nxt1 to RNA results in silencing of target loci and the concomitant accumulation of repressive chromatin marks. Nxf2 and Panx proteins are mutually required for proper localization and stability. We mapped the protein domains crucial for the Nxf2/Panx complex formation and show that the amino-terminal portion of Panx is sufficient to induce transcriptional silencing.
Data availability
Sequencing data reported in this paper has been deposited in GEO under accession number GSE121661. Mass Spectrometry data has been deposited to the PRIDE Archive (accession number PXD011415)
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piRNA-guided co-transcriptional silencing coopts nuclear export factorsNCBI Gene Expression Omnibus, GSE121661.
Article and author information
Author details
Funding
Wellcome (Investigator award 110161/Z/15/Z)
- Gregory J Hannon
Cancer Research UK
- Gregory J Hannon
European Molecular Biology Organization (Long-Term Fellowship ALTF 1015-2017)
- Filippo Ciabrelli
Boehringer Ingelheim Fonds (PhD fellowship)
- Marzia Munafò
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Torben Heick Jensen, Aarhus University, Denmark
Publication history
- Received: April 26, 2019
- Accepted: June 19, 2019
- Accepted Manuscript published: June 20, 2019 (version 1)
- Version of Record published: August 2, 2019 (version 2)
Copyright
© 2019, Fabry et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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piRNA-guided co-transcriptional silencing coopts nuclear export factors
eLife 8:e47999.
https://doi.org/10.7554/eLife.47999
Further reading
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- Chromosomes and Gene Expression
- Neuroscience
Sensory feedback is required for the stable execution of learned motor skills, and its loss can severely disrupt motor performance. The neural mechanisms that mediate sensorimotor stability have been extensively studied at systems and physiological levels, yet relatively little is known about how disruptions to sensory input alter the molecular properties of associated motor systems. Songbird courtship song, a model for skilled behavior, is a learned and highly structured vocalization that is destabilized following deafening. Here, we sought to determine how the loss of auditory feedback modifies gene expression and its coordination across the birdsong sensorimotor circuit. To facilitate this system-wide analysis of transcriptional responses, we developed a gene expression profiling approach that enables the construction of hundreds of spatially-defined RNA-sequencing libraries. Using this method, we found that deafening preferentially alters gene expression across birdsong neural circuitry relative to surrounding areas, particularly in premotor and striatal regions. Genes with altered expression are associated with synaptic transmission, neuronal spines, and neuromodulation and show a bias toward expression in glutamatergic neurons and Pvalb/Sst-class GABAergic interneurons. We also found that connected song regions exhibit correlations in gene expression that were reduced in deafened birds relative to hearing birds, suggesting that song destabilization alters the inter-region coordination of transcriptional states. Finally, lesioning LMAN, a forebrain afferent of RA required for deafening-induced song plasticity, had the largest effect on groups of genes that were also most affected by deafening. Combined, this integrated transcriptomics analysis demonstrates that the loss of peripheral sensory input drives a distributed gene expression response throughout associated sensorimotor neural circuitry and identifies specific candidate molecular and cellular mechanisms that support the stability and plasticity of learned motor skills.
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- Chromosomes and Gene Expression
In songbirds, deafening leads to changes in gene expression which have now been mapped at the single-cell level across the neural circuit involved in song production.
