Extended Data Fig. 10: Features of DDX-19, NPP-14, and GLEL-1 Regulated Small RNAs and Working Model.

(a) Analysis of small RNA length and first nucleotide distribution in WT, ddx-19(-), npp-14(-), and glel-1(-) animals. (b) Biotype analysis of genes with significantly upregulated or downregulated targeting small RNAs in ddx-19(-), npp-14(-), and glel-1(-) animals compared with WT. (c) Representative factor analysis of genes with altered small RNAs in ddx-19(-), npp-14(-), and glel-1(-) animals against CSR-1, HRDE-1, and WAGO target lists. (d) piRNA target analysis of genes with altered small RNAs in ddx-19(-), npp-14(-), and glel-1(-) animals compared with WT. Welch’s t-test. (e) Comparison of genes with altered small RNAs in ddx-19(-), npp-14(-), and glel-1(-) animals with those in prg-1(-) or mut-16(-) mutants¹⁸. (f) Working Model. Biomolecular condensates are networks formed through protein-protein and protein-RNA interactions. Their organization depends on competing protein-protein interactions⁷⁰. Homotypic interactions drive liquid-liquid phase separation, while non-competing heterotypic interactions result in co-phase separation, and competing heterotypic interactions lead to multiphase condensates⁷¹. In WT animals, the germline D compartment is anchored to the nuclear pore by NPP-14 and GLEL-1 at the cytoplasmic filament. This compartment is localized at the base of PZMS compartments, where NPP-14/GLEL-1 and P granules compete for DDX-19 interaction, facilitating D compartment formation. Loss of NPP-14 or GLEL-1 disrupts DDX-19 interactions, causing the D compartment to mix with P or Z compartments. This destabilizes the PZMS compartments, enlarging them and increasing local ZNFX-1 concentration. The elevated ZNFX-1 levels interact with more pUG RNAs, redistributing them from the M compartment to the mixed compartment and extending transgenerational epigenetic inheritance. This graph was created in BioRender. Deng, B. (2025) https://BioRender.com/w67i892.