miRNA–target chimeras reveal miRNA 3′-end pairing as a major determinant of Argonaute target specificity

microRNAs (miRNAs) act as sequence-specific guides for Argonaute (AGO) proteins. By using a modified AGO HITS-CLIP strategy that enriches miRNAs ligated to their endogenous mRNA targets, here the authors show that miRNA 3' end pairing is a general determinant of AGO binding specificity.