Reduced insulin/IGF-1 signaling restores germ cell immortality to Caenorhabditis elegans Piwi mutants

Matt Simon; Peter Sarkies; Kohta Ikegami; Anna-Lisa Doebley; Leonard D Goldstein; Jacinth Mitchell; Aisa Sakaguchi; Eric A Miska; Shawn Ahmed

doi:10.1016/j.celrep.2014.03.056

Reduced insulin/IGF-1 signaling restores germ cell immortality to Caenorhabditis elegans Piwi mutants

Cell Rep. 2014 May 8;7(3):762-73. doi: 10.1016/j.celrep.2014.03.056. Epub 2014 Apr 24.

Authors

Matt Simon¹, Peter Sarkies², Kohta Ikegami³, Anna-Lisa Doebley³, Leonard D Goldstein², Jacinth Mitchell¹, Aisa Sakaguchi⁴, Eric A Miska⁵, Shawn Ahmed⁶

Affiliations

¹ Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
² The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
³ Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
⁴ Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵ The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: [email protected].
⁶ Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Argonaute Proteins
Caenorhabditis elegans Proteins
Forkhead Transcription Factors
Insulin
PRG-1 protein, C elegans
RNA, Small Interfering
Transcription Factors
daf-16 protein, C elegans
Insulin-Like Growth Factor I
Oxidoreductases, N-Demethylating
DAF-2 protein, C elegans
Receptor, Insulin

Abstract

Publication types

MeSH terms

Substances

Grants and funding