Three germline lncRNAs promote PUM protein condensation and germline differentiation

Long-non-coding RNAs (lncRNAs) are highly expressed in gonads yet, given the lack of fertility defects in most knockouts, their role is unclear. Here, we report the overlapping roles of three lncRNAs in Caenorhabditis elegans fertility, whereby they bind and sequester FBF-2, an inhibitor of germ-cell differentiation. Deletion of the lncRNAs leads to additive reduction in progenitor-cells and progeny. FBF-2 destabilizes mRNAs, and in the lncRNAs deletion strain, the level of these mRNAs is significantly lower. FBF-2 is present in germ-cells, both diffused in the cytoplasm and in peri-nuclear condensates, and lncRNAs deletion reduces FBF-2 condensation. Moreover, the deletion reduces FBF-2 association to P granules, evolutionarily conserved phase-separated condensates. Our work demonstrates that lncRNAs cooperate to establish optimal fertility; hence the full effect is only evident in multiple knockouts. These findings support a model that the lncRNAs spatially restricts pro-proliferation factors into phase-separated granules and release mRNAs required for differentiation. Comparative transcriptomics between WT and fbf-2 mutants and between WT and a mutant in 3 lincRNA genes Compartive transcriptomics between fbf-1 and fbf-1Xtriple mutants