RRC ID 45857
Author Simon M, Sarkies P, Ikegami K, Doebley AL, Goldstein LD, Mitchell J, Sakaguchi A, Miska EA, Ahmed S.
Title Reduced insulin/IGF-1 signaling restores germ cell immortality to Caenorhabditis elegans Piwi mutants.
Journal 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.
Volume 7(3)
Pages 762-73
Published 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
Times Cited 45
C.elegans tm872