Transposase concentration controls transposition activity: Myth or reality?

• 3 profiles depict experimental data about transposase overproduction inhibition.
• The 3 profiles are the LEIA, the OPI sensu stricto and the STATOC.
• Differences between the 3 profiles would be due to protein co-factors.
• Overexpression of a transposase leads to its cytoplasm or nucleolus prison.
• The sequestration mode in cytoplasm or nucleoli is known to each transposase.

Deciphering the mechanisms underlying the regulation of DNA transposons might be central to understanding their function and dynamics in genomes. From results obtained under artificial experimental conditions, it has been proposed that some DNA transposons self-regulate their activity via overproduction inhibition (OPI), a mechanism by which transposition activity is down-regulated when the transposase is overconcentrated in cells. However, numerous studies have given contradictory results depending on the experimental conditions. Moreover, we do not know in which cellular compartment this phenomenon takes place, or whether transposases assemble to form dense foci when they are highly expressed in cells.In the present review, we focus on investigating the data available about eukaryotic transposons to explain the mechanisms underlying OPI. Data in the literature indicate that members of the IS630-Tc1-mariner, Hobo-Ac-Tam, and piggyBac superfamilies are able to use OPI to self-regulate their transposition activity in vivo in most eukaryotic cells, and that some of them are able to assemble so as to form higher order soluble oligomers. We also investigated the localization and behavior of GFP-fused transposases belonging to the mariner, Tc1-like, and piggyBac families, investigating their ability to aggregate in cells when they are overexpressed. Transposases are able to form dense foci when they are highly expressed. Moreover, the cellular compartments in which these foci are concentrated depend on the transposase, and on its expression. The data presented here suggest that sequestration in cytoplasmic or nucleoplasmic foci, or within the nucleoli, might protect the genome against the potentially genotoxic effects of the non-specific nuclease activities of eukaryotic transposases.