RRC ID |
45857
|
著者 |
Simon M, Sarkies P, Ikegami K, Doebley AL, Goldstein LD, Mitchell J, Sakaguchi A, Miska EA, Ahmed S.
|
タイトル |
Reduced insulin/IGF-1 signaling restores germ cell immortality to Caenorhabditis elegans Piwi mutants.
|
ジャーナル |
Cell Rep
|
Abstract |
Defects in the Piwi/piRNA pathway lead to transposon desilencing and immediate sterility in many organisms. We found that the C. elegans Piwi mutant prg-1 became sterile after growth for many generations. This phenotype did not occur for RNAi mutants with strong transposon-silencing defects and was separable from the role of PRG-1 in transgene silencing. Brief periods of starvation extended the transgenerational lifespan of prg-1 mutants by stimulating the DAF-16/FOXO longevity transcription factor. Constitutive activation of DAF-16 via reduced daf-2 insulin/IGF-1 signaling immortalized prg-1 strains via RNAi proteins and histone H3 lysine 4 demethylases. In late-generation prg-1 mutants, desilencing of repetitive segments of the genome occurred, and silencing of repetitive loci was restored in prg-1; daf-2 mutants. This study reveals an unexpected interface between aging and transgenerational maintenance of germ cells, where somatic longevity is coupled to a genome-silencing pathway that promotes germ cell immortality in parallel to the Piwi/piRNA system.
|
巻・号 |
7(3)
|
ページ |
762-73
|
公開日 |
2014-5-8
|
DOI |
10.1016/j.celrep.2014.03.056
|
PII |
S2211-1247(14)00253-8
|
PMID |
24767993
|
PMC |
PMC4049074
|
MeSH |
Animals
Argonaute Proteins / antagonists & inhibitors
Argonaute Proteins / genetics*
Argonaute Proteins / metabolism
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / antagonists & inhibitors
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Forkhead Transcription Factors
Germ Cells / cytology
Germ Cells / metabolism*
Insulin / metabolism*
Insulin-Like Growth Factor I / metabolism*
Oxidoreductases, N-Demethylating / metabolism
RNA Interference
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Receptor, Insulin / deficiency
Receptor, Insulin / genetics
Receptor, Insulin / metabolism
Signal Transduction
Transcription Factors / metabolism
|
IF |
8.109
|
引用数 |
45
|
WOS 分野
|
CELL BIOLOGY
|
リソース情報 |
線虫 |
tm872 |