Abstract
The C. elegans TRIM-NHL protein NHL-2 functions as a co-factor for the microRNA Induced Silencing Complex (miRISC) and thereby enhances the post-transcriptional repression of several genetically verified microRNA targets, including hbl-1 and let-60/Ras (by the let-7-family of microRNAs) and cog-1 (by the lsy-6 microRNA). NHL-2 is localized to cytoplasmic processing bodies (P-bodies) and physically associates with the P-body protein CGH-1 and the core miRISC components ALG-1/2 and AIN-1. nhl-2 and cgh-1mutations compromise the repression of microRNA targets in vivo, but do not affect microRNA biogenesis, indicating a role for a NHL-2-CGH-1 complex in the effector phase of miRISC activity. We propose that the NHL-2-CGH-1 complex functions in association with mature miRISC to modulate the efficacy of microRNA:target interactions in response to physiological and developmental signals, and thereby helps ensure the robustness of genetic regulatory pathways regulated by microRNAs.