The Multiplicity of Argonaute Complexes in Mammalian Cells

Argonautes (AGOs) are a highly conserved family of proteins found in most eukaryotes and involved in mechanisms of gene regulation, both at the transcriptional and post-transcriptional level. Among other functions, AGO proteins associate with microRNAs (miRNAs) to mediate the post-transcriptional repression of protein-coding genes. In this process, AGOs associate with members of the trinucleotide repeat containing 6 protein (TNRC6) family to form the core of the RNA-induced silencing complex (RISC), the effector machinery that mediates miRNA function. However, the description of the exact composition of the RISC has been a challenging task due to the fact the AGO's interactome is dynamically regulated in a cell type- and condition-specific manner. Here, we summarize some of the most significant studies that have identified AGO complexes in mammalian cells, as well as the approaches used to characterize them. Finally, we discuss possible opportunities to exploit what we have learned on the properties of the RISC to develop novel anti-cancer therapies.

Automated summary

Argonautes (AGOs) are highly conserved proteins involved in gene regulation at the transcriptional and post-transcriptional level. They associate with microRNAs to mediate post-transcriptional repression of protein-coding genes. The exact composition of AGO complexes, which form the core of the RNA-induced silencing complex (RISC), has been challenging to determine due to dynamic regulation. This review summarizes studies on AGO complexes in mammalian cells and discusses opportunities for developing novel anti-cancer therapies based on the properties of RISC.