PiggyBac Transposable Element Derived 5 explained

PiggyBac Transposable Element Derived 5 is an enzyme that in humans is encoded by the PGBD5 gene.[1] PGBD5 is a DNA transposase related to the ancient PiggyBac transposase first identified in the cabbage looper moth, Trichoplusia ni.[2] The gene is believed to have been domesticated over 500 million years ago in the common ancestor of cephalochordates and vertebrates.[3] The putative catalytic triad of the protein composed of three aspartic acid residues is conserved among PGBD5-like genes through evolution, and is distinct from other PiggyBac-like genes.[3] PGBD5 has been shown to be able to transpose DNA in a sequence-specific, cut-and-paste fashion.[4] PGBD5 has also been proposed to mediate site-specific DNA rearrangements in human tumors.[5]

Human PGBD5 can mobilize the insect PiggyBac transposons in human cell culture.[6]

Expression in the brain

In mature mice brain tissue PGBD5 is found primarily in regions of the olfactory bulb, hippocampus, and cerebellum. In embryonic mice brain tissue PGBD5 is found not only in the medial pallium and prepontine isthmus, which are embryonic brain areas that give rise to the development of the hippocampus and cerebellum but also in areas in the embryonic brain that give rise to the hypothalamus and medulla.[7]

Disease Associations

PGBD5 is expressed in the majority of human pediatric solid tumors.[8] It's upregulated in sporadic Creutzfeldt-Jakob disease.[9] PGBD5 is associated with frontotemporal dementia, where it gets most expressed in neurons, followed by ogliodendrocytes, mature astrocytes, fetal astrocytes, endothelial cells and then microglia/macrophages.[10]

Notes and References

  1. Web site: PGBD5 piggyBac transposable element derived 5 [Homo sapiens (human)] - Gene - NCBI]. www.ncbi.nlm.nih.gov. 8 April 2017.
  2. Toman J . A course to pursue . Nursing Times. 1979 . 75 . 17 . 694–695 . 255260.
  3. Pavelitz T, Gray LT, Padilla SL, Bailey AD, Weiner AM . PGBD5: a neural-specific intron-containing piggyBac transposase domesticated over 500 million years ago and conserved from cephalochordates to humans . Mobile DNA . 4 . 1 . 23 . November 2013 . 24180413 . 10.1186/1759-8753-4-23 . 3902484 . free .
  4. Henssen AG, Henaff E, Jiang E, Eisenberg AR, Carson JR, Villasante CM, Ray M, Still E, Burns M, Gandara J, Feschotte C, Mason CE, Kentsis A . Genomic DNA transposition induced by human PGBD5 . eLife . 4 . September 2015 . 26406119 . 10.7554/eLife.10565 . 4625184 . free .
  5. Henssen AG, Koche R, Zhuang J, Jiang E, Reed C, Eisenberg A, Still E, MacArthur IC, Rodríguez-Fos E, Gonzalez S, Puiggròs M, Blackford AN, Mason CE, de Stanchina E, Gönen M, Emde AK, Shah M, Arora K, Reeves C, Socci ND, Perlman E, Antonescu CR, Roberts CW, Steen H, Mullen E, Jackson SP, Torrents D, Weng Z, Armstrong SA, Kentsis A . PGBD5 promotes site-specific oncogenic mutations in human tumors . Nature Genetics . 49 . 7 . 1005–1014 . July 2017 . 28504702 . 5489359 . 10.1038/ng.3866 .
  6. Ivics. Zoltán. May 2016. Endogenous Transposase Source in Human Cells Mobilizes piggyBac Transposons. Molecular Therapy. en. 24. 5. 851–854. 10.1038/mt.2016.76. 4881781. 27198853.
  7. Shao. Benjamin. May 2018. Effects of PiggyBac Transposable Element Derived 5 (PGBD5) in Cortical Tissue. BS thesis. University of Connecticut.
  8. Research. American Association for Cancer. 2018-01-01. The DNA Transposase PGBD5 Sensitizes Tumors to Inhibition of DNA Repair. Cancer Discovery. en. 8. 1. OF17. 10.1158/2159-8290.CD-RW2017-213. 2159-8274. 29127084.
  9. Vastrad . Basavaraj . Vastrad . Chanabasayya . Kotturshetti . Iranna . 2020-12-24 . Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses . en . 10.1101/2020.12.21.20248688v1.
  10. Broce. Iris. Karch. Celeste M.. Wen. Natalie. Fan. Chun C.. Wang. Yunpeng. Tan. Chin Hong. Kouri. Naomi. Ross. Owen A.. Höglinger. Günter U.. Muller. Ulrich. Hardy. John. 2018-01-09. Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies. PLOS Medicine. en. 15. 1. e1002487. 10.1371/journal.pmed.1002487. 1549-1676. 5760014. 29315334 . free .

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