Two SID-1-dependent genes sensitive to heritable epigenetic changes can also impact reproduction

Abstract

Import of double-stranded RNA (dsRNA) into the germ line can have consequences that last for many generations. However, the role of such transgenerational regulation by extracellular dsRNA is unclear. In the nematode C. elegans, entry of dsRNA into the cytosol requires the transmembrane protein SID-1 and loss of SID-1 for a few generations causes changes in gene expression that can persist for hundreds of generations. Here we report an expanded number of such SID-1-dependent genes (SDGs) and analyze two germline-expressed SDGs: sdg-1 and sdg-2. Deleting sdg-1 reduces brood size in some lineages. An endogenous SDG-1::mCherry fusion protein shows conditional enrichment within nuclei, colocalization with perinuclear germ granules, and colocalization with microtubules. Although animals with SDG-1::mCherry have a normal brood size, they have fewer early progeny with some animals showing defective germline morphology. Deleting the sdg-1 open reading frame eliminates defects in most but not all the animals that express mCherry in a now sdg-1(-) background, suggesting transgenerational consequences of SDG-1::mCherry that persist in some siblings lacking sdg-1. Deleting sdg-2 also reduces brood size in some lineages. An endogenous SDG-2::mCherry fusion protein is constitutively detectable in the cytoplasm and nucleus. The sequence and predicted structure of SDG-2 suggest that it can interact with the Gli-type transcription factor TRA-1, which regulates spermatogenesis. Together, these results suggest that changes in SDG-1 or SDG-2 can impact reproduction. Therefore, the import of extracellular dsRNA or other SID-1 function(s) that regulate SDGs could have evolved to modulate the lingering impacts of ancestral epigenetic changes.