Reference - Detail
| RRC ID | 45592 |
|---|---|
| Author | Leopold LE, Heestand BN, Seong S, Shtessel L, Ahmed S. |
| Title | Lack of pairing during meiosis triggers multigenerational transgene silencing in Caenorhabditis elegans. |
| Journal | Proc Natl Acad Sci U S A |
| Abstract |
Single-copy transgenes in Caenorhabditis elegans can be subjected to a potent, irreversible silencing process termed small RNA-induced epigenetic silencing (RNAe). RNAe is promoted by the Piwi Argonaute protein PRG-1 and associated Piwi-interacting RNAs (piRNAs), as well as by proteins that promote and respond to secondary small interfering RNA (siRNA) production. Here we define a related siRNA-mediated silencing process, termed "multigenerational RNAe," which can occur for transgenes that are maintained in a hemizygous state for several generations. We found that transgenes that contain either GFP or mCherry epitope tags can be silenced via multigenerational RNAe, whereas a transgene that possesses GFP and a perfect piRNA target site can be rapidly and permanently silenced via RNAe. Although previous studies have shown that PRG-1 is typically dispensable for maintenance of RNAe, we found that both initiation and maintenance of multigenerational RNAe requires PRG-1 and the secondary siRNA biogenesis protein RDE-2. Although silencing via RNAe is irreversible, we found that transgene expression can be restored when hemizygous transgenes that were silenced via multigenerational RNAe become homozygous. Furthermore, multigenerational RNAe was accelerated when meiotic pairing of the chromosome possessing the transgene was abolished. We propose that persistent lack of pairing during meiosis elicits a reversible multigenerational silencing response, which can lead to permanent transgene silencing. Multigenerational RNAe may be broadly relevant to single-copy transgenes used in experimental biology and to shaping the epigenomic landscape of diverse species, where genomic polymorphisms between homologous chromosomes commonly result in unpaired DNA during meiosis. |
| Volume | 112(20) |
| Pages | E2667-76 |
| Published | 2015-5-19 |
| DOI | 10.1073/pnas.1501979112 |
| PII | 1501979112 |
| PMID | 25941370 |
| PMC | PMC4443339 |
| MeSH | ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism Animals Argonaute Proteins / genetics Argonaute Proteins / metabolism Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism DNA Primers / genetics Gene Silencing / physiology* Green Fluorescent Proteins / genetics Luminescent Proteins / genetics Meiosis / physiology* Microscopy, Fluorescence Microscopy, Interference RNA, Small Interfering / genetics Red Fluorescent Protein Transgenes / genetics* |
| IF | 9.412 |
| Times Cited | 8 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm872 tm574 tm1813 |