RRC ID |
46005
|
著者 |
Adamo A, Woglar A, Silva N, Penkner A, Jantsch V, La Volpe A.
|
タイトル |
Transgene-mediated cosuppression and RNA interference enhance germ-line apoptosis in Caenorhabditis elegans.
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ジャーナル |
Proc Natl Acad Sci U S A
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Abstract |
Introduction of multiple copies of a germ-line-expressed gene elicits silencing of the corresponding endogenous gene during Caenorhabditis elegans oogenesis; this process is referred to as germ-line cosuppression. Transformed plasmids assemble into extrachromosomal arrays resembling extra minichromosomes with repetitive structures. Loss of the transgene extrachromosomal array leads to reversion of the silencing phenomenon. Cosuppression and RNAi depend upon some of the same genes. In the C. elegans germ line, about half the cells undergo a physiological programmed cell death that shares most genetic requirements with somatic apoptosis. In addition, apoptosis is stimulated by DNA damage and synaptic failure mediated through different apoptotic checkpoints. We found that both germ-line cosuppression and RNAi of germ-line-expressed genes enhance apoptosis during C. elegans oogenesis. In contrast, apoptosis is not enhanced by extrachromosomal arrays carrying genes not driven by germ-line-specific promoters that thus do not elicit transgene-mediated cosuppression/silencing. Similarly, introduction of doubled-stranded RNA that shares no homology with endogenous genes has no effect on apoptosis. "Silencing-induced apoptosis" is dependent upon sir-2.1 and cep-1 (the worm p53 ortholog), and is accompanied by a rise in RAD-51 foci, a marker for ongoing DNA repair, indicating induction of DNA double-strand breaks. This finding suggests that the DNA damage-response pathway is involved. RNAi and cosuppression have been postulated as defense mechanisms against genomic intruders. We speculate that the mechanism here described may trigger the elimination of germ cells that have undergone viral infection or transposon activation.
|
巻・号 |
109(9)
|
ページ |
3440-5
|
公開日 |
2012-2-28
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DOI |
10.1073/pnas.1107390109
|
PII |
1107390109
|
PMID |
22331911
|
PMC |
PMC3295272
|
MeSH |
Animals
Apoptosis / genetics*
Caenorhabditis elegans / cytology
Caenorhabditis elegans / genetics*
Caenorhabditis elegans Proteins / physiology
DNA Repair
Extrachromosomal Inheritance
Gene Dosage
Germ Cells / pathology
Germ-Line Mutation
Meiosis / genetics
Mutagenesis, Insertional
Plasmids / genetics
RNA Interference*
RNA, Double-Stranded / genetics
Rad51 Recombinase / physiology
Sirtuins / physiology
Transgenes
Tumor Suppressor Protein p53 / physiology
|
IF |
9.412
|
引用数 |
8
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
線虫 |
tm1298 |