Investigating the Role of the NHL-2 RNA-Binding Domain in the C. elegans Germline

NHL-2 is a conserved TRIM-NHL RNA-binding protein required for normal gene regulation, fertility, and development in Caenorhabditis elegans. This study demonstrates that NHL-2 is essential for transgenerational epigenetic inheritance and that its RNA-binding activity is essential to its function. RNA-binding mutants exhibited defects comparable to those of the null mutant and disrupted normal localisation of NHL-2 to germline perinuclear P bodies, while also enlarging somatic P bodies. TurboID proteomics identified 121 NHL-2-associated proteins, including IFET-1 and CCR4-NOT components, linking NHL-2 to translational repression and mRNA deadenylation. Together, these findings suggest that NHL-2 functions as a regulator of RNA partitioning, condensate dynamics, and epigenetic inheritance.