The C-terminal Domain of piggyBac Transposase Is Not Required for DNA Transposition

PiggyBac(PB)-like elements (pble) are members of a eukaryotic DNA transposon family. This family is of interest to evolutionary genomics because pble transposases have been domesticated at least 9 times in vertebrates. The amino acid sequence of pble transposases can be split into three regions: an acidic N-terminal domain (similar to 100 aa), a central domain (similar to 400 aa) containing a DD[D/E] catalytic triad, and a cysteine-rich domain (CRD; similar to 90 aa). Two recent reports suggested that a functional CRD is required for pble transposase activity. Here we found that two CRD-deficient pble transposases, a PB variant and an isoform encoded by the domesticated PB-derived vertebrate transposase gene 5 (pgbd5) trigger transposition of the Ifp2 pble. When overexpressed in HeLa cells, these CRD-deficient transposases can insert Ifp2 elements with proper and improper transposon ends, associated with deleterious effects on cells. Finally, we found that mouse CRD-deficient transposase Pgbd5, as well as PB, do not insert pbles at random into chromosomes. Transposition events occurred more often in genic regions, in the neighbourhood of the transcription start sites and were often found in genes predominantly expressed in the human central nervous system. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The pble transposase family, of interest in evolutionary genomics, has been domesticated multiple times in vertebrates. CRD-deficient pble transposases can trigger transposition and have deleterious effects on cells. These transposition events occur more often in genic regions, near transcription start sites, and in genes predominantly expressed in the human central nervous system.