PRC, UMR INRA-CNRS 7247, Centre INRA Val de Loire, 37380 Nouzilly Cedex, France.
Gene. 2013 Nov 10;530(2):165-71. doi: 10.1016/j.gene.2013.08.039. Epub 2013 Aug 28.
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.
解析 DNA 转座子调控机制对于理解其在基因组中的功能和动态可能至关重要。根据人工实验条件下获得的结果，有人提出一些 DNA 转座子通过过度产生抑制（OPI）来自我调节其活性，即当转座酶在细胞中过度浓缩时，转座活性下调的机制。然而，许多研究根据实验条件得出了相互矛盾的结果。此外，我们不知道这种现象发生在细胞的哪个区室，或者当转座酶在细胞中高度表达时是否会组装成密集的焦点。在本综述中，我们专注于研究有关真核转座子的现有数据，以解释 OPI 的机制。文献中的数据表明，IS630-Tc1-mariner、Hobo-Ac-Tam 和 piggyBac 超家族的成员能够在大多数真核细胞中利用 OPI 来自我调节其转座活性，并且其中一些成员能够组装成更高阶的可溶性寡聚物。我们还研究了属于 mariner、Tc1 样和 piggyBac 家族的 GFP 融合转座酶的定位和行为，研究了当它们过表达时在细胞中聚集的能力。转座酶在高表达时能够形成密集的焦点。此外，这些焦点集中的细胞区室取决于转座酶及其表达。这里呈现的数据表明，在细胞质或核质焦点中或核仁内的隔离可能会保护基因组免受真核转座酶非特异性核酸酶活性的潜在遗传毒性影响。
