Fraternity of old-timers: How ubiquitin regulates miRNA functions

miRNA-mediated gene repression and ubiquitin-dependent processes are among the oldest and most versatile mechanisms that control multiple molecular pathways, rather than just protein turnover. These systems were discovered decades ago and have become among the most studied. All systems within cells are interconnected, and these two are no exception: the plethora of studies have demonstrated that the activity of the miRNAs system depends on players of the ubiquitin-centered universe of processes, and vice versa. This review focuses on recent progress that highlights that very similar mechanisms of regulation of miRNAs by ubiquitin-related processes are likely to be found in distantly related species, including animals, plants, and viruses. Most of them occur through the ubiquitination of Argonaute proteins, but some of the other miRNA system factors are also regulated. This suggests that their regulatory relationships are either ancient evolutionary acquisitions or have arisen independently in different kingdoms.