What are Argonaute proteins and why are they important for miRNA detection?

Argonaute (AGO) proteins are the core structural proteins of the RISC complex — they physically hold the miRNA guide strand and perform the mRNA silencing activity. In humans, there are four Argonaute proteins (AGO1–4), with AGO2 being the primary effector. Some circulating cell-free miRNAs are found bound to AGO2 proteins outside of exosomes, which contributes to their stability in blood and urine. The presence of AGO2-bound miRNA complexes in circulation is one reason miRNA-based liquid biopsy is feasible. Importantly, the Yenos osmium-tagging chemistry works on the free miRNA strand itself — the osmium metalorganic probe attaches to the miRNA nucleobases before nanopore analysis.