This template was adapted from the original submission. Edits were made to enhance scientific accuracy, optimal usability and/or to meet industry-leading design standards for science communication. MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as guide molecules in RNA silencing. The miRNA:target interaction usually occurs at the 5′ end of the miRNA (the ‘seed’ region). In the last few years, it has emerged that there is a special class of targets which bind the miRNA not only through the seed, but also through a second region of complementarity at the 3′ end of the miRNA. The extended complementarity forces the miRNA out of Ago2, where it becomes accessible to enzymatic degradation.