title: Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations.
abstract: Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility. Increased expression of repetitive loci occurred in both germ and somatic cells of late-generation rsd mutant adults, suggesting that desilencing of many heterochromatic segments of the genome contributes to sterility. Nuclear RNAi defective (NRDE)-2 promotes nuclear silencing in response to exogenous double-stranded RNA, and our data imply that RSD-2, RSD-6, and NRDE-2 function in a common transgenerational nuclear silencing pathway that responds to endogenous siRNAs. We propose that RSD-2 and RSD-6 promote germ cell immortality at stressful temperatures by maintaining transgenerational epigenetic inheritance of endogenous siRNA populations that promote genome silencing.
authors.affiliation: Departments of Genetics and Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan; and.
authors.forename: Aisa
authors.initials: A
authors.lastname: Sakaguchi
authors.affiliation: The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Sarkies
authors.affiliation: Departments of Genetics and Biology, Curriculum in Genetics and Molecular Biology, and.
authors.forename: Matt
authors.initials: M
authors.lastname: Simon
authors.affiliation: Biology.
authors.forename: Anna-Lisa
authors.initials: AL
authors.lastname: Doebley
authors.affiliation: The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Goldstein
authors.affiliation: Biology.
authors.forename: Ashley
authors.initials: A
authors.lastname: Hedges
authors.affiliation: Biology.
authors.forename: Kohta
authors.initials: K
authors.lastname: Ikegami
authors.affiliation: Departments of Genetics and Seeding Postdoctoral Innovators in Research and Education Postdoctoral Fellowship Program, University of North Carolina, Chapel Hill, NC 27599;
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Alvares
authors.affiliation: Departments of Genetics and.
authors.forename: Liwei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Biology.
authors.forename: Jeannine R
authors.initials: JR
authors.lastname: LaRocque
authors.affiliation: Biology.
authors.forename: Julie
authors.initials: J
authors.lastname: Hall
authors.affiliation: The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom shawn@med.unc.edu eam29@cam.ac.uk.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Miska
authors.affiliation: Departments of Genetics and Biology, Curriculum in Genetics and Molecular Biology, and shawn@med.unc.edu eam29@cam.ac.uk.
authors.forename: Shawn
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D020090:Chromosome Segregation; D005786:Gene Expression Regulation; D020868:Gene Silencing; D056426:Genetic Loci; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D007246:Infertility; D009154:Mutation; D009630:Nondisjunction, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism*; D013091:Spermatogenesis; D013312:Stress, Physiological; D020080:Tandem Repeat Sequences / Q000235:genetics; D013696:Temperature; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D034741:RNA, Small Interfering; C529657:RSD-2 protein, C elegans; C529658:RSD-6 protein, C elegans
keywords: fertility; germ line; tudor domain protein