How RNA interference is controlled
RNA interference (RNAi) is a complex system of cellular regulation that researchers are still trying to fully comprehend. Recent evidence suggests that Argonaute (AGO) proteins control RNAi in the cell, but the mechanisms of this control are not very clear. The EU-funded PASRNA project investigated one possible mechanism: post-translational modifications (PTMs) of the AGO proteins. PTMs are changes that happen to a protein after it is produced by the cell, usually as a way to 'switch on' or 'switch off' the activity of that protein. PASRNA investigated the phosphorylation and ubiquitination of AGO, two of the most common PTMs. Researchers managed to identify a specific location on the AGO protein where phosphorylation takes place. It is in the functional core of the protein where it binds to various types of RNA, suggesting that phosphorylation affects AGO function. PASRNA then tested this in human immune cells, where RNAi plays an important role. When these cells were exposed to pathogens, AGO was phosphorylated rapidly (within an hour) and then phosphorylation slowly decreased over time. An investigation into ubiquitination of AGO was less conclusive. Researchers did however find an enzyme that is responsible for ubiquitinating AGO. Overall, the research of PASRNA has confirmed that AGO control of RNAi occurs through PTMs of the AGO protein in response to external stimuli. This improves our knowledge of RNA biology and will have knock-on effects for human, animal and plant health.
