Three lncRNAs promote PUM protein condensation and germline differentiation.

Abstract

Long non-coding RNAs (lncRNAs) are abundant in gonads, yet most knockout models show no fertility defects, leaving their role unclear. Here, we identify overlapping functions of three lncRNAs in Caenorhabditis elegans fertility. These lncRNAs bind and sequester FBF-2, a regulator that inhibits germ cell differentiation. Combined deletion of the lncRNAs reduces progenitor cell number and overall progeny, reflecting additive effects. In lncRNA mutants, pro-meiotic transcripts-normally destabilized by FBF-2-are significantly reduced. FBF-2 localizes to both the cytoplasm and peri-nuclear condensates in germ cells, but its peri-nuclear condensation and association with P granules-phase-separated, evolutionarily conserved structures-are diminished in lncRNA mutants. Our findings suggest that these lncRNAs cooperatively promote fertility by spatially restricting FBF-2 within granules, thus reducing its activity and allowing the expression of differentiation-promoting transcripts. The requirement for multiple knockouts to reveal this phenotype highlights the redundancy and combinatorial function of lncRNAs in regulating germline development.