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Human Endogenous Retrovirus K (HERV-K) can drive gene expression as a promoter in Caenorhabditis elegans

  • Durnaoglu, Serpen (Department of Life Science, Hanyang University) ;
  • Kim, Heui-Soo (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Ahnn, Joohong (Department of Life Science, Hanyang University) ;
  • Lee, Sun-Kyung (Department of Life Science, Hanyang University)
  • 투고 : 2020.07.15
  • 심사 : 2020.08.20
  • 발행 : 2020.10.31

초록

Endogenous retroviruses (ERVs) are retrotransposons present in various metazoan genomes and have been implicated in metazoan evolution as well as in nematodes and humans. The long terminal repeat (LTR) retrotransposons contain several regulatory sequences including promoters and enhancers that regulate endogenous gene expression and thereby control organismal development and response to environmental change. ERVs including the LTR retrotransposons constitute 8% of the human genome and less than 0.6% of the Caenorhabditis elegans (C. elegans) genome, a nematode genetic model system. To investigate the evolutionarily conserved mechanism behind the transcriptional activity of retrotransposons, we generated a transgenic worm model driving green fluorescent protein (GFP) expression using Human endogenous retroviruses (HERV)-K LTR as a promoter. The promoter activity of HERV-K LTR was robust and fluorescence was observed in various tissues throughout the developmental process. Interestingly, persistent GFP expression was specifically detected in the adult vulva muscle. Using deletion constructs, we found that the region from positions 675 to 868 containing the TATA box was necessary for promoter activity driving gene expression in the vulva. Interestingly, we found that the promoter activity of the LTR was dependent on che-1 transcription factor, a sensory neuron driver, and lin-15b, a negative regulator of RNAi and germline gene expression. These results suggest evolutionary conservation of the LTR retrotransposon activity in transcriptional regulation as well as the possibility of che-1 function in non-neuronal tissues.

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참고문헌

  1. Craig NL, Craigie R, Gellert M and Lambowitz Alan M (2015) Mobile DNA III, ASM Press, Washington, D.C. 1051-1078
  2. Bessereau JL (2006) Transposons in C. elegans; in, The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.70.1
  3. Subramanian RP, Wildschutte JH, Russo C and Coffin JM (2011) Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses. Retrovirology 8, 90 https://doi.org/10.1186/1742-4690-8-90
  4. Vargiu L, Rodriguez-Tome P, Sperber GO et al (2016) Classification and characterization of human endogenous retroviruses; mosaic forms are common. Retrovirology 13, 7 https://doi.org/10.1186/s12977-015-0232-y
  5. Kim HS (2012) Genomic impact, chromosomal distribution and transcriptional regulation of HERV elements. Mol Cells 33, 539-544 https://doi.org/10.1007/s10059-012-0037-y
  6. Garcia-Montojo M, Doucet-O'Hare T, Henderson L and Nath A (2018) Human endogenous retrovirus-K (HML-2): a comprehensive review. Crit Rev Microbiol 44, 715-738 https://doi.org/10.1080/1040841X.2018.1501345
  7. Galli UM, Sauter M, Lecher B et al (2005) Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors. Oncogene 24, 3223-3228 https://doi.org/10.1038/sj.onc.1208543
  8. Li M, Radvanyi L, Yin B et al (2017) Downregulation of human endogenous retrovirus type K (HERV-K) viral env RNA in pancreatic cancer cells decreases cell proliferation and tumor growth. Clin Cancer Res 23, 5892-5911 https://doi.org/10.1158/1078-0432.CCR-17-0001
  9. Shin W, Lee J, Son S-Y, Ahn K, Kim H-S and Han K (2013) Human-specific HERV-K insertion causes genomic variations in the human genome. PloS One 8, e60605 https://doi.org/10.1371/journal.pone.0060605
  10. Lee W-C, Kim D-Y, Kim M-J et al (2019) Delay of cell growth and loss of stemness by inhibition of reverse transcription in human mesenchymal stem cells derived from dental tissue. Anim Cells Syst (Seoul) 23, 335-345 https://doi.org/10.1080/19768354.2019.1651767
  11. Bourque G, Leong B, Vega VB et al (2008) Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Res 18, 1752-1762 https://doi.org/10.1101/gr.080663.108
  12. Ou SH, Wu F, Harrich D, Garcia-Martinez LF and Gaynor RB (1995) Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. J Virol 69, 3584-3596 https://doi.org/10.1128/JVI.69.6.3584-3596.1995
  13. Li W, Lee MH, Henderson L et al (2015) Human endogenous retrovirus-K contributes to motor neuron disease. Sci Transl Med 7, 307ra153 https://doi.org/10.1126/scitranslmed.aac8201
  14. Mitra J, Guerrero EN, Hegde PM et al (2019) Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects. Proc Natl Acad Sci U S A 116, 4696-4705 https://doi.org/10.1073/pnas.1818415116
  15. Krug L, Chatterjee N, Borges-Monroy R et al (2017) Retrotransposon activation contributes to neurodegeneration in a Drosophila TDP-43 model of ALS. PLoS Genet 13, e1006635 https://doi.org/10.1371/journal.pgen.1006635
  16. Ash PEA, Zhang YJ, Roberts CM et al (2010) Neurotoxic effects of TDP-43 overexpression in C. elegans. Hum Mol Genet 19, 3206-3218 https://doi.org/10.1093/hmg/ddq230
  17. Saldi TK, Ash PEA, Wilson G et al (2014) TDP-1, the Caenorhabditis elegans ortholog of TDP-43, limits the accumulation of double-stranded RNA. EMBO J 33, 2947-2966 https://doi.org/10.15252/embj.201488740
  18. Macfarlan TS, Gifford WD, Agarwal S et al (2011) Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A. Genes Dev 25, 594-607 https://doi.org/10.1101/gad.2008511
  19. Ganko EW, Fielman KT and McDonald JF (2001) Evolutionary history of Cer elements and their impact on the C. elegans genome. Genome Res 11, 2066-2074 https://doi.org/10.1101/gr.196201
  20. Rho M, Choi J-H, Kim S, Lynch M and Tang H (2007) De novo identification of LTR retrotransposons in eukaryotic genomes. BMC genomics 8, 90 https://doi.org/10.1186/1471-2164-8-90
  21. Fischer SEJ and Ruvkun G (2020) Caenorhabditis elegans ADAR editing and the ERI-6/7/ MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons. Proc Natl Acad Sci U S A 117, 5987-5996 https://doi.org/10.1073/pnas.1919028117
  22. Ni JZ, Kalinava N, Mendoza SG and Gu SG (2018) The spatial and temporal dynamics of nuclear RNAi-targeted retrotransposon transcripts in Caenorhabditis elegans. Development 145, dev167346 https://doi.org/10.1242/dev.167346
  23. Dennis S, Sheth U, Feldman JL, English KA and Priess JR (2012) C. elegans germ cells show temperature and agedependent expression of Cer1, a Gypsy/Ty3-related retrotransposon. PLoS Pathog 8, e1002591 https://doi.org/10.1371/journal.ppat.1002591
  24. Kwon S, Kim EJE, Lee SJV (2018) Mitochondria-mediated defense mechanisms against pathogens in Caenorhabditis elegans. BMB Rep 51, 274-279 https://doi.org/10.5483/BMBRep.2018.51.6.111
  25. Etchberger JF, Lorch A, Sleumer MC et al (2007) The molecular signature and cis-regulatory architecture of a C. elegans gustatory neuron. Genes Dev 21, 1653-1674 https://doi.org/10.1101/gad.1560107
  26. Boxem M and van den Heuvel S (2002) C. elegans class B synthetic multivulva genes act in G(1) regulation. Curr Biol 12, 906-911 https://doi.org/10.1016/S0960-9822(02)00844-8
  27. Clouaire T, Roussigne M, Ecochard V, Mathe C, Amalric F and Girard J-P (2005) The THAP domain of THAP1 is a large C2CH module with zinc-dependent sequence-specific DNA-binding activity. Proc Natl Acad Sci U S A 102, 6907-6912 https://doi.org/10.1073/pnas.0406882102
  28. Roussigne M, Kossida S, Lavigne A-C et al (2003) The THAP domain: a novel protein motif with similarity to the DNA-binding domain of P element transposase. Trends Biochem Sci 28, 66-69 https://doi.org/10.1016/S0968-0004(02)00013-0
  29. Majorek KA, Dunin-Horkawicz S, Steczkiewicz K et al (2014) The RNase H-like superfamily: new members, comparative structural analysis and evolutionary classification. Nucleic Acids Res 42, 4160-4179 https://doi.org/10.1093/nar/gkt1414
  30. Moelling K, Broecker F, Russo G and Sunagawa S (2017) RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense. Front Microbiol 8, 1745-1745 https://doi.org/10.3389/fmicb.2017.01745
  31. Lehner B, Calixto A, Crombie C et al (2006) Loss of LIN-35, the Caenorhabditis elegans ortholog of the tumor suppressor p105Rb, results in enhanced RNA interference. Genome Biol 7, R4 https://doi.org/10.1186/gb-2006-7-1-r4
  32. Wang D, Kennedy S, Conte D et al (2005) Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants. Nature 436, 593-597 https://doi.org/10.1038/nature04010
  33. Wu X, Shi Z, Cui M, Han M and Ruvkun G (2012) Repression of Germline RNAi Pathways in Somatic Cells by Retinoblastoma Pathway Chromatin Complexes. PLoS Genet 8, e1002542 https://doi.org/10.1371/journal.pgen.1002542
  34. Rechtsteiner A, Costello ME, Egelhofer TA, Garrigues JM, Strome S and Petrella LN (2019) Repression of Germline Genes in Caenorhabditis elegans Somatic Tissues by H3K9 Dimethylation of Their Promoters. Genetics 212, 125-140 https://doi.org/10.1534/genetics.118.301878