Small RNA-Directed Silencing: The Fly Finds Its Inner Fission Yeast?

RNA Therapeutics Institute, Howard Hughes Medical Institute, and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Current biology: CB (Impact Factor: 9.57). 04/2013; 23(8):R318-20. DOI: 10.1016/j.cub.2013.03.033
Source: PubMed


Several recent studies demonstrate that piRNAs guide Piwi protein to repress transposon transcription in fly ovaries, much as fission yeast use siRNAs to silence repeat sequences. Still mysterious though is how Piwi targets euchromatic transposons for silencing, but not the specialized heterochromatic loci that produce piRNA precursors.

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    • "At least two nuclear proteins (Maelstrom and Gtsf1) have been identified as putative Piwi cofactors in transcriptional silencing (11,19–21). It is thought that Piwi binds to nascent RNA via its piRNA guide and recruits H3K9 histone methyltransferase to target genomic loci, similarly to AGO1-mediated repression in S. pombe (22). It is generally accepted that H3K9 methylation results in HP1 binding that leads to the establishment of heterochromatic state, preventing transcription (23). "
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    ABSTRACT: The Piwi-interacting RNA (piRNA)-interacting Piwi protein is involved in transcriptional silencing of transposable elements in ovaries of Drosophila melanogaster. Here we characterized the genome-wide effect of nuclear Piwi elimination on the presence of the heterochromatic H3K9me3 mark and HP1a, as well as on the transcription-associated mark H3K4me2. Our results demonstrate that a significant increase in the H3K4me2 level upon nuclear Piwi loss is not accompanied by the alterations in H3K9me3 and HP1a levels for several germline-expressed transposons, suggesting that in this case Piwi prevents transcription by a mechanism distinct from H3K9 methylation. We found that the targets of Piwi-dependent chromatin repression are mainly related to the elements that display a higher level of H3K4me2 modification in the absence of silencing, i.e. most actively transcribed elements. We also show that Piwi-guided silencing does not significantly influence the chromatin state of dual-strand piRNA-producing clusters. In addition, host protein-coding gene expression is essentially not affected due to the nuclear Piwi elimination, but we noted an increase in small nuclear spliceosomal RNAs abundance and propose Piwi involvement in their post-transcriptional regulation. Our work reveals new aspects of transposon silencing in Drosophila, indicating that transcription of transposons can underpin their Piwi dependent silencing, while canonical heterochromatin marks are not obligatory for their repression.
    Nucleic Acids Research 04/2014; 42(10). DOI:10.1093/nar/gku268 · 9.11 Impact Factor
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    ABSTRACT: The PIWI-interacting RNA (piRNA) pathway is a small RNA silencing system that keeps selfish genetic elements such as transposons under control in animal gonads. Several lines of evidence indicate that nuclear PIWI family proteins guide transcriptional silencing of their targets, yet the composition of the underlying silencing complex is unknown. Here we demonstrate that the double CHHC zinc finger protein gametocyte-specific factor 1 (Gtsf1) is an essential factor for Piwi-mediated transcriptional repression in Drosophila. Cells lacking Gtsf1 contain nuclear Piwi loaded with piRNAs, yet Piwi's silencing capacity is ablated. Gtsf1 interacts directly with a small subpool of nuclear Piwi, and loss of Gtsf1 phenocopies loss of Piwi in terms of deregulation of transposons, loss of H3K9 trimethylation (H3K9me3) marks at euchromatic transposon insertions, and deregulation of genes in proximity to repressed transposons. We propose that only a small fraction of nuclear Piwi is actively engaged in target silencing and that Gtsf1 is an essential component of the underlying Piwi-centered silencing complex.
    Genes & development 08/2013; 27(15):1693-705. DOI:10.1101/gad.221150.113 · 10.80 Impact Factor
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    ABSTRACT: The discovery of millions of PIWI-interacting RNAs revealed a fascinating and unanticipated dimension of biology. The PIWI-piRNA pathway has been commonly perceived as germline-specific, even though the somatic function of PIWI proteins was documented when they were first discovered. Recent studies have begun to re-explore this pathway in somatic cells in diverse organisms, particularly lower eukaryotes. These studies have illustrated the multifaceted somatic functions of the pathway not only in transposon silencing but also in genome rearrangement and epigenetic programming, with biological roles in stem-cell function, whole-body regeneration, memory and possibly cancer.
    Nature 01/2014; 505(7483):353-9. DOI:10.1038/nature12987 · 41.46 Impact Factor
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