NRDE-1 is required for germline immortality.

Abstract

NRDE-1 is required germline immortality and is a critical component of the transcriptional silencing pathway known as nuclear RNAi. Loss of the nrde-1 gene activity results in progressive accumulation of transgenerational stress which compromises the germline tissue and results in germ cell loss, ending ultimately in sterility. Using nrde-1, we paint a sketch of a germline stress and identify DAF-2, a component of the insulin signaling pathway, as well as piRNAs as significant contributors to this stress. Additionally, we explore the accumulation of stress by defining the developmental stage at which the sterility occurs. Due to its role in silencing, we conducted RNAseq on early vs sterile generation nrde-1 mutant animals to investigate the cause of its Germline Mortality and outline results in the expression of selfish genetic elements such as retrotransposons. Although these elements are expressed in sterile generation nrde-1 they were similarly upregulated in another nrde mutant that does not become sterile. Additionally, we have uncovered a list of 19 genes whose transcription is >2 fold upregulated in late generation nrde-1mutants that have accrued damage. Of these genes 42% correspond to the process of spermatogenesis, in agreement with other Mrt studies involving epigenetic transgenerational sterility. We explain this by showing that sperm are not necessary for sterility and that developmental delay occurs and may explain spermatogenesis gene misregulation.Doctor of Philosoph