Abstract

Over the last decades, it has become evident that highly complex networks of regulators govern post‐transcriptional regulation of gene expression. A novel class of Argonaute (Ago)‐associated RNA molecules, the agotrons, was recently shown to function in a Drosha‐ and Dicer‐independent manner, hence bypassing the maturation steps required for canonical microRNA (miRNA) biogenesis. Agotrons are found in most mammals and associate with Ago as ∼100 nucleotide (nt) long RNA species. Here, we speculate on the functional and biological relevance of agotrons: (i) agotrons could serve as non‐promiscuous miRNA‐like regulators with reduced off‐targeting or (ii) agotrons could encompass other putative functions, such as protecting Ago proteins from taking up aberrant short RNAs or by rescuing and stabilizing otherwise unloaded Ago‐proteins from degradation. Collectively, agotrons have emerged as a novel class of interesting non‐coding RNA molecules, but their full functional potential and biological impact still remain to be disclosed.