[en] The vertebrate piggyBac derived transposase 5 (PGBD5) encodes a domesticated transposase, which is active and able to transpose its distantly related piggyBac-like element (pble), Ifp2. This raised the question whether PGBD5 would be more effective at mobilizing a phylogenetically closely related pble element. We aimed to identify the pble most closely related to the pgbd5 gene. We updated the landscape of vertebrate pgbd genes to develop efficient filters and identify the most closely related pble to each of these genes. We found that Tcr-pble is phylogenetically the closest pble to the pgbd5 gene. Furthermore, we evaluated the capacity of two murine and human PGBD5 isoforms, Mm523 and Hs524, to transpose both Tcr-pble and Ifp2 elements. We found that both pbles could be transposed by Mm523 with similar efficiency. However, integrations of both pbles occurred through both proper transposition and improper PGBD5-dependent recombination. This suggested that the ability of PGBD5 to bind both pbles may not be based on the primary sequence of element ends, but may involve recognition of inner DNA motifs, possibly related to palindromic repeats. In agreement with this hypothesis, we identified internal palindromic repeats near the end of 24 pble sequences, which display distinct sequences.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Helou, Laura ; Université de Liège - ULiège > Département des sciences cliniques ; UMR INRAE 0085, CNRS 7247, Physiologie de la Reproduction et des Comportements, Centre INRA Val de Loire, 37380 Nouzilly, France
Beauclair, Linda; UMR INRAE 0085, CNRS 7247, Physiologie de la Reproduction et des Comportements, Centre INRA Val de Loire, 37380 Nouzilly, France
Dardente, Hugues; UMR INRAE 0085, CNRS 7247, Physiologie de la Reproduction et des Comportements, Centre INRA Val de Loire, 37380 Nouzilly, France
Piégu, Benoît; UMR INRAE 0085, CNRS 7247, Physiologie de la Reproduction et des Comportements, Centre INRA Val de Loire, 37380 Nouzilly, France
Tsakou-Ngouafo, Louis; UMR MEPHI D-258, I, IRD, Aix Marseille Université, 19-21 Boulevard Jean Moulin, 13005 Marseille, France, CNRS SNC 5039, 13005 Marseille, France
Lecomte, Thierry; EA GICC 7501, CHRU de Tours, 37044 TOURS Cedex 09, France
Kentsis, Alex; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, Cornell University, New York, NY, USA, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Pontarotti, Pierre; UMR INRAE 0085, CNRS 7247, Physiologie de la Reproduction et des Comportements, Centre INRA Val de Loire, 37380 Nouzilly, France, CNRS SNC 5039, 13005 Marseille, France
Bigot, Yves; UMR INRAE 0085, CNRS 7247, Physiologie de la Reproduction et des Comportements, Centre INRA Val de Loire, 37380 Nouzilly, France. Electronic address: yves.bigot@inrae.fr
Language :
English
Title :
The piggyBac-derived protein 5 (PGBD5) transposes both the closely and the distantly related piggyBac-like elements Tcr-pble and Ifp2.
SNFGE - Société Nationale Française de Gastro-Entérologie [FR] Merck [DE] Ligue Nationale Contre le Cancer [FR] Region Centre-Val de Loire [FR]
Funding text :
This work was supported by the C.N.R.S., the I.N.R.A., and the GDR CNRS 2157. It also received funds from a research program grants from the Ligue Nationale Contre le Cancer, the Merck foundation, and the French National Society of Gastroenterology. Laura Helou holds a PhD fellowship from the Région Centre Val de Loire. We acknowledge the high-throughput sequencing facilities of I2BC for its sequencing and bioinformatics expertize. Alex Kentsis is a consultant for Novartis and is supported by the National Cancer Institute grants R01 CA214812 and P30 CA008748. Yves Bigot, who was in charge of the achievement of this project does not have to thank the French National Research Agency for its financial support but he kindly thanks it for the excellent reviews embellished with arguments based on scientific and cultural novelties in the expertise of his yearly application file during the last decade. Our thanks to Peter Arensburger at California Polytechnic University in Pomona CA (Cal Poly Pomona) for reviewing the manuscript for legibility.This work was supported by the C.N.R.S. the I.N.R.A. and the GDR CNRS 2157. It also received funds from a research program grants from the Ligue Nationale Contre le Cancer, the Merck foundation, and the French National Society of Gastroenterology. Laura Helou holds a PhD fellowship from the R?gion Centre Val de Loire. We acknowledge the high-throughput sequencing facilities of I2BC for its sequencing and bioinformatics expertize. Alex Kentsis is a consultant for Novartis and is supported by the National Cancer Institute grants R01 CA214812 and P30 CA008748. Yves Bigot, who was in charge of the achievement of this project does not have to thank the French National Research Agency for its financial support but he kindly thanks it for the excellent reviews embellished with arguments based on scientific and cultural novelties in the expertise of his yearly application file during the last decade. Our thanks to Peter Arensburger at California Polytechnic University in Pomona CA (Cal Poly Pomona) for reviewing the manuscript for legibility. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Piégu, B., Bire, S., Arensburger, P., Bigot, Y., A survey of transposable element classification systems - a call for a fundamental update to meet the challenge of their diversity and complexity. Mol. Phylogenet. Evol. 86 (2015), 90–109.
Fraser, M.J., Smith, G.E., Summers, M.D., Acquisition of host cell DNA sequences by baculoviruses: relationship between host DNA insertions and FP mutants of Autographa californica and Galleria mellonella nu- clear polyhedrosis viruses. J. Virol. 47 (1983), 287–300.
Mitra, R., Fain-Thornton, J., Craig, N.L., piggyBac can bypass DNA syn- thesis during cut and paste transposition. EMBO J. 27 (2008), 1097–1109.
Mitra, R., Li, X., Kapusta, A., Mayhew, D., Mitra, R.D., Feschotte, C., Craig, N.L., Functional characterization of piggyBat from the bat Myotis lucifugus unveils an active mammalian DNA transposon. Proc. Nat. Acad. Sci. USA 110 (2013), 234–239.
Bouallègue, M., Rouault, J.D., Hua-Van, A., Makni, M., Capy, P., Molecular evolution of piggyBac superfamily: from selfishness to domestication. Gen. Biol. Evol. 9 (2017), 323–339.
Morellet, N., Li, X., Wieninger, S.A., Taylor, J.L., Bischerour, J., Moriau, S., Lescop, E., Bardiaux, B., et al. Sequence-specific DNA binding activity of the cross-brace zinc finger motif of the piggyBac transposase. Nucl. Acids. Res. 46 (2018), 2660–2677.
Sinzelle, L., Izsvák, Z., Ivics, Z., Molecular domestication of transposable elements: from detrimental parasites to useful host genes. Cell. Mol. Life. Sci. 66 (2009), 1073–1093.
Joly-Lopez, Z., Bureau, T.E., Exaptation of transposable element coding sequences. Curr. Opin. Genet. Dev. 49 (2018), 34–42.
Huang, S., Tao, X., Yuan, S., Zhang, Y., Li, P., Beilinson, H.A., Zhang, Y., Yu, W., et al. Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination. Cell 166 (2016), 102–114.
Zhang, Y., Cheng, T.C., Huang, G., Lu, Q., Surleac, M.D., Mandell, J.D., Pontarotti, P., Petrescu, A.J., et al. Transposon molecular domestication and the evolution of the RAG recombinase. Nature 569 (2019), 79–84.
Kapitonov, V.V., Jurka, J., RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS. Biol., 3, 2005, e181.
Sarkar, A., Sim, C., Hong, Y.S., Hogan, J.R., Fraser, M.J., Robertson, H.M., Collins, F.H., Molecular evolutionary analysis of the widespread piggyBac transposon family and related “domesticated” sequences. Mol. Genet. Genom. 270 (2003), 173–180.
Pavelitz, T., Gray, L.T., Padilla, S.L., Bailey, A.D., Weiner, A.M., PGBD5: a neural-specific intron containing piggyBac transposase domesticated over 500 million years ago and conserved from cephalochordates to humans. Mob. DNA 4 (2013), 23–39.
Delsuc, F., Brinkmann, H., Chourrout, D., Philippe, H., Tunicates and not cephalochordates are the closest living relatives of vertebrates. Nature. 439 (2006), 965–968.
Putnam, N.H., Butts, T., Ferrier, D.E.K., Furlong, R.F., Hellsten, U., Kawashima, T., Robinson-Rechavi, M., Shoguchi, E., et al. The amphioxus genome and the evolution of the chordate karyotype. Nature 453 (2008), 1064–1071.
Henssen, A.G., Henaff, E., Jiang, E., Eisenberg, A.R., Carson, J.R., Villasante, C.M., Ray, M., Still, E., et al. Genomic DNA transposition induced by human PGBD5. Elife., 4, 2015, e10565.
Henssen, A.G., Koche, R., Zhuang, J., Jiang, E., Reed, C., Eisenberg, A., Still, E., MacArthur, I.C., et al. PGBD5 promotes site-specific oncogenic mutations in human tumors. Nature Genet. 49 (2017), 1005–1014.
Kryazhimskiy, S., Plotkin, J.B., The Population Genetics of dN/dS. PLoS. Genet., 4, 2008, e1000304.
Inoue, Y., Saga, T., Aikawa, T., Kumagai, M., Shimada, A., Kawaguchi, Y., Naruse, K., Morishita, S., et al. Complete fusion of a transposon and herpesvirus created the Teratorn mobile element in medaka fish. Nature Commun., 8, 2017, 551.
Arkhipova, I.R., Yushenova, I.A., Giant transposons in eukaryotes: is bigger better?. Gen. Biol. Evol. 11 (2019), 906–918.
Hikosaka, A., Kobayashi, T., Saito, Y., Kawahara, A., Evolution of the Xenopus piggyBac transposon family TxpB: domesticated and untamed strategies of transposon subfamilies. Mol. Biol. Evol. 24 (2007), 2648–2656.
Henssen, A.G., Reed, C., Jiang, E., Garcia, H.D., von Stebut, J., MacArthur, I.C., Hundsdoerfer, P., Kim, J.H., et al. Therapeutic targeting of PGBD5-induced DNA repair dependency in pediatric solid tumors. Sci. Transl. Med., 9, 2017, eaam9078.
Elick, T.A., Lobo, N., Fraser, M.J. Jr., Analysis of the cis-acting DNA elements required for piggyBac transposable element excision. Mol. Gen. Genet. 255 (1997), 605–610.
Li, M.A., Pettitt, S.J., Eckert, S., Ning, Z., Rice, S., Cadiñanos, J., Yusa, K., Conte, N., et al. The piggyBac transposon displays local and distant reintegration preferences and can cause mutations at noncanonical integration sites. Mol. Cell. Biol. 33 (2013), 1317–1330.
Wang, H., Mayhew, D., Chen, X., Johnston, M., Mitra, R.D., “Calling cards” for DNA-binding proteins in mammalian cells. Genetics. 190 (2012), 941–949.
Wu, M., Sun, Z.C., Hu, C.L., Zhang, G.F., Han, Z.J., An active piggyBac-like element in Macdunnoughia crassisigna. Insect. Sci. 15 (2008), 521–528.
Daimon, T., Mitsuhira, M., Katsuma, S., Abe, H., Mita, K., Shimada, T., Recent transposition of yabusame, a novel piggybac-like transposable element in the genome of the silkworm, Bombyx mori. Genome 53 (2010), 585–593.
Troyanovsky, B., Bitko, V., Pastukh, V., Fouty, B., Solodushko, V., The Functionality of Minimal PiggyBac Transposons in Mammalian Cells. Mol. Ther. Nucleic. Acids, 5, 2016, e369.
Chen, Q., Luo, W., Veach, R.A., Hickman, A.B., Wilson, M.H., Dyda, F., Structural basis of seamless excision and specific targeting by piggyBac transposase. Nature Commun., 11, 2020, 3446.
Brázda, V., Laister, R.C., Jagelská, E.B., Arrowsmith, C., Cruciform structures are a common DNA feature important for regulating biological processes. BMC Mol. Biol., 12, 2011, 33.
Kaushik, M., Kaushik, S., Roy, K., Singh, A., Mahendru, S., Kumar, M., Chaudhary, S., Ahmed, S., et al. A bouquet of DNA structures: Emerging diversity. Biochem. Biophys. Rep. 5 (2016), 388–395.
Guiblet, W.M., Cremona, M.A., Cechova, M., Harris, R.S., Kejnovská, I., Kejnovsky, E., Eckert, K., Chiaromonte, F., et al. Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate. Gen. Res. 28 (2018), 1767–1778.
Nakanishi, H., Higuchi, Y., Kawakami, S., Yamashita, F., Hashida, M., Comparison of piggyBac transposition efficiency between linear and circular donor vectors in mammalian cells. J. Biotechnol. 154 (2011), 205–208.
Bao, W., Kojima, K.K., Kohany, O., Repbase Update, a database of repetitive elements in eukaryotic genomes. Mob. DNA., 6, 2015, 11.
Simossis, V.A., Heringa, J., The PRALINE online server: Optimising progressive multiple alignment on the web. Comput. Biol. Chem. 27 (2003), 511–519.
Sander, C., Schneider, R., Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins 9 (1991), 56–68.
Rost, B., Twilight zone of protein sequence alignments. Prot. Engin. 12 (1999), 85–94.
Stamatakis, A., RAxML version 8: A tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinform. 30 (2014), 1312–1313.
Suyama, M., Torrents, D., Bork, P., PAL2NAL: robust conversion of protein sequence alignments into the corresponding codon alignments. Nucl. Acids. Res. 34 (2006), W609–W612.
Yang, Z., PAML 4: phylogenetic analysis by maximum likelihood. Mol. Biol. Evol. 24 (2007), 1586–1591.
Cer, R.Z., Donohue, D.E., Mudunuri, U.S., Temiz, N.A., Loss, M.A., Starner, N.J., Halusa, G.N., Volfovsky, N., et al. Non-B DB v2.0: a database of predicted non-B DNA-forming motifs and its associated tools. Nucl. Acids. Res. 41 (2013), D94–D100.
Myers, E.W., Miller, W., Optimal alignments in linear space. Comput. Appl. Biosci. 4 (1988), 11–17.
Travnickova-Bendova, Z., Cermakian, N., Reppert, S.M., Sassone-Corsi, P., Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity. Proc. Natl. Acad. Sci. USA 99 (2002), 7728–7733.
Bire, S., Ley, D., Casteret, S., Mermod, N., Bigot, Y., Rouleux-Bonnin, F., Optimization of the piggyBac transposon using mRNA and insulators: toward a more reliable gene delivery system. PLoS. One., 8, 2013, e82559.
Bire, S., Casteret, S., Piégu, B., Beauclair, L., Moiré, N., Arensbuger, P., Bigot, Y., Mariner transposons contain a silencer: possible role of the polycomb repressive complex 2. PLoS. Genet., 12, 2016, e1005902.
Bartholomae, C.C., Glimm, H., von Kalle, C., Schmidt, M., Insertion site pattern: global approach by linear amplification-mediated PCR and mass sequencing. Meth. Mol. Biol. 859 (2012), 255–265.
Bolger, A.M., Lohse, M., Usadel, B., Trimmomatic: a flexible trimmer for illumina sequence data. Bioinformatics 30 (2014), 2114–2120.
Li, H., Durbin, R., Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26 (2010), 589–595.
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., 1000 Genome Project Data Processing Subgroup, et al. The Sequence alignment/map (SAM) format and SAMtools. Bioinformatics 25 (2009), 2078–2079.
Quinlan, A.R., HallI, M., BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 26 (2010), 841–842.
Layer, R.M., Chiang, C., Quinlan, A.R., Hall, I.M., LUMPY: a probabilistic framework for structural variant discovery. Gen. Biol., 15, 2014, R84.
