Most miRNA plots we follow share a similar climactic ending: miRNA inhibits this, in this condition, in response to this. Don’t get us wrong. We can read about miRNA regulation all day, which is good because we often do, but do you ever wonder what happens to miRNAs after they’ve locked their target, and put a halt to translation?
A team of researchers from the Friedrich Miescher Institute for Biomedical Research in Switzerland decided to look into what happens next. In Nature last week, they provided us with some additional footage in the miRNA regulatory story when they documented a mechanism where miRNAs are removed from miRISC and degraded by XRN-2…allowing the whole miRNA process to start over again.
The Swiss team found that, in C. elegans, the exoribonuclese XRN-2 facilitates miRNA release from Argonaute complexes and is in charge of miRNA degradation. Their experiments led them to some other interesting tidbits of info:
- XRN-2 mediates miRNA turnover in vivo and in vitro
- XRN-2 modulates miRNA activity in vivo
- miRNA degradation and turnover helps maintain proper miRNA levels
- The presence of target RNA prevents Argonaute:miRNA separation and degradation; pointing to a coordination of miRNA and target RNA levels
All of this paints a new picture of the miRNA life cycle – Like a merry-go-round where one miRNA gets off (and is degraded), and a new one gets on and goes around until its journey is complete. The authors also note that not all miRNAs tested in vivo followed the same pattern, so they predict that there may be other undiscovered regulatory proteins out there guiding differential turnover of miRNAs.