Details

Autor(en) / Beteiligte

• Sakaguchi, Aisa
• Sarkies, Peter
• Simon, Matt
• Doebley, Anna-Lisa
• Goldstein, Leonard D
• Hedges, Ashley
• Ikegami, Kohta
• Alvares, Stacy M
• Yang, Liwei
• LaRocque, Jeannine R
• Hall, Julie
• Miska, Eric A
• Ahmed, Shawn

Titel

Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2014-10, Vol.111 (41), p.E4323-E4331

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Significance Here, we establish a role for small RNAs in promoting transgenerational fertility via an endogenous temperature-sensitive silencing process that is promoted by the RNAi spreading defective (RSD)-2 and RSD-6 proteins, which have been implicated in RNA interference in response to exogenous double-stranded RNA triggers. This process could be broadly relevant to transgenerational maintenance of heterochromatin and is plausibly relevant to regulation of aging of somatic cells as they proliferate. 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.