A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress
- University of Cambridge, United Kingdom
- The Gurdon Institute, United Kingdom
Abstract
Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means.
Data availability
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A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stressPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE87524).
Article and author information
Author details
Funding
Wellcome (54523)
- Julie Ahringer
Wellcome (101863)
- Julie Ahringer
Canadian Institutes of Health Research
- Alicia N McMurchy
Cancer Research UK (C13474/A18583)
- Eric A Miska
Human Frontier Science Program
- Alexandra Sapetschnig
Wellcome (104640/Z/14/Z)
- Eric A Miska
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Edith Heard, Institut Curie, France
Version history
- Received: September 20, 2016
- Accepted: March 10, 2017
- Accepted Manuscript published: March 15, 2017 (version 1)
- Version of Record published: April 18, 2017 (version 2)
- Version of Record updated: October 5, 2017 (version 3)
Copyright
© 2017, McMurchy 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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A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress
eLife 6:e21666.
https://doi.org/10.7554/eLife.21666
Further reading
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- Chromosomes and Gene Expression
Splicing is the stepwise molecular process by which introns are removed from pre-mRNA and exons are joined together to form mature mRNA sequences. The ordering and spatial distribution of these steps remain controversial, with opposing models suggesting splicing occurs either during or after transcription. We used single-molecule RNA FISH, expansion microscopy, and live-cell imaging to reveal the spatiotemporal distribution of nascent transcripts in mammalian cells. At super-resolution levels, we found that pre-mRNA formed clouds around the transcription site. These clouds indicate the existence of a transcription-site-proximal zone through which RNA move more slowly than in the nucleoplasm. Full-length pre-mRNA undergo continuous splicing as they move through this zone following transcription, suggesting a model in which splicing can occur post-transcriptionally but still within the proximity of the transcription site, thus seeming co-transcriptional by most assays. These results may unify conflicting reports of co-transcriptional versus post-transcriptional splicing.
