Highlights d Germline and somatic miRNA silencing complexes differ in composition d Germline miRNAs protect from degradation rather than destabilize targeted transcripts d Germline miRNA targeting leads to mRNA perinuclear localization adjacent to P granules d Repression of germline miRNA targets is dependent on the P granule component GLH-1

Among the different types of small RNAs, microRNAs (miRNAs) are key players in controlling gene expression at the mRNA level. To be active, they must associate with an Argonaute protein to form the miRNA induced silencing complex (miRISC) and binds to specific mRNA through complementarity sequences. The miRISC binding to an mRNA can lead to multiple outcomes, the most frequent being inhibition of the translation and/or deadenylation followed by decapping and mRNA decay. In the last years, several studies described different mechanisms modulating miRISC functions in animals. For instance, the regulation of the Argonaute protein through post-translational modifications can change the miRISC gene regulatory activity as well as modulate its binding to proteins, mRNA targets and miRISC stability. Furthermore, the presence of RNA binding proteins and multiple miRISCs at the targeted mRNA 3 0 untranslated region (3 0 UTR) can also affect its function through cooperation or competition mechanisms, underlying the importance of the 3 0 UTR environment in miRNA-mediated repression. Another way to regulate the miRISC function is by modulation of its interactors, forming different types of miRNA silencing complexes that affect gene regulation differently. It is also reported that the subcellular localization of several components of the miRNA pathway can modulate miRISC function, suggesting an important role for vesicular trafficking in the regulation of this essential silencing complex.