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Enhancer Function of MicroRNA-3681 Derived from Long Terminal Repeats Represses the Activity of Variable Number Tandem Repeats in the 3' UTR of SHISA7

  • Lee, Hee-Eun (Department of Integrated Biological Science, Pusan National University) ;
  • Park, Sang-Je (National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Huh, Jae-Won (National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Imai, Hiroo (Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University) ;
  • Kim, Heui-Soo (Institute of Systems Biology, Pusan National University)
  • Received : 2020.03.04
  • Accepted : 2020.05.27
  • Published : 2020.07.31

Abstract

microRNAs (miRNAs) are non-coding RNA molecules involved in the regulation of gene expression. miRNAs inhibit gene expression by binding to the 3' untranslated region (UTR) of their target gene. miRNAs can originate from transposable elements (TEs), which comprise approximately half of the eukaryotic genome and one type of TE, called the long terminal repeat (LTR) is found in class of retrotransposons. Amongst the miRNAs derived from LTR, hsa-miR-3681 was chosen and analyzed using bioinformatics tools and experimental analysis. Studies on hsa-miR-3681 have been scarce and this study provides the relative expression analysis of hsa-miR-3681-5p from humans, chimpanzees, crab-eating monkeys, and mice. Luciferase assay for hsa-miR-3681-5p and its target gene SHISA7 supports our hypothesis that the number of miRNA binding sites affects target gene expression. Especially, the variable number tandem repeat (VNTR) and hsa-miR-3681-5p share the binding sites in the 3' UTR of SHISA7, which leads the enhancer function of hsamiR-3681-5p to inhibit the activity of VNTR. In conclusion, hsa-miR-3681-5p acts as a super-enhancer and the enhancer function of hsa-miR-3681-5p acts as a repressor of VNTR activity in the 3' UTR of SHISA7.

Keywords

References

  1. Agarwal, V., Bell, G.W., Nam, J.W., and Bartel, D.P. (2015). Predicting effective microRNA target sites in mammalian mRNAs. Elife 4, e05005.
  2. Agren, J.A. and Clark, A.G. (2018). Selfish genetic elements. PLoS Genet. 14, e1007700. https://doi.org/10.1371/journal.pgen.1007700
  3. Ambros, V., Bartel, B., Bartel, D.P., Burge, C.B., Carrington, J.C., Chen, X., Dreyfuss, G., Eddy, S.R., Griffiths-Jones, S., Marshall, M., et al. (2003). A uniform system for microRNA annotation. RNA 9, 277-279. https://doi.org/10.1261/rna.2183803
  4. Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297. https://doi.org/10.1016/S0092-8674(04)00045-5
  5. Bourque, G., Burns, K.H., Gehring, M., Gorbunova, V., Seluanov, A., Hammell, M., Imbeault, M., Izsvak, Z., Levin, H.L., Macfarlan, T.S., et al. (2018). Ten things you should know about transposable elements. Genome Biol. 19, 199. https://doi.org/10.1186/s13059-018-1577-z
  6. Brummer, A. and Hausser, J. (2014). MicroRNA binding sites in the coding region of mRNAs: extending the repertoire of post-transcriptional gene regulation. Bioessays 36, 617-626. https://doi.org/10.1002/bies.201300104
  7. Cai, H., Zhu, X.X., Li, Z.F., Zhu, Y.P., and Lang, J.H. (2018). MicroRNA dysregulation and steroid hormone receptor expression in uterine tissues of rats with endometriosis during the implantation window. Chin. Med. J. (Engl). 131, 2193-2204. https://doi.org/10.4103/0366-6999.240808
  8. Feschotte, C. (2008). Transposable elements and the evolution of regulatory networks. Nat. Rev. Genet. 9, 397-405. https://doi.org/10.1038/nrg2337
  9. Gonzalez-Cao, M., Iduma, P., Karachaliou, N., Santarpia, M., Blanco, J., and Rosell, R. (2016). Human endogenous retroviruses and cancer. Cancer Biol. Med. 13, 483-488. https://doi.org/10.20892/j.issn.2095-3941.2016.0080
  10. Gu, W., Xu, Y., Xie, X., Wang, T., Ko, J.H., and Zhou, T. (2014). The role of RNA structure at 5' untranslated region in microRNA-mediated gene regulation. RNA 20, 1369-1375. https://doi.org/10.1261/rna.044792.114
  11. Hall, T.A. (1999). BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp. Ser. 41, 95-98.
  12. Han, W., Li, J., Pelkey, K.A., Pandey, S., Chen, X., Wang, Y.X., Wu, K., Ge, L., Li, T., Castellano, D., et al. (2019). Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions. Science 366, 246-250. https://doi.org/10.1126/science.aax5719
  13. Hausser, J., Syed, A.P., Bilen, B., and Zavolan, M. (2013). Analysis of CDSlocated miRNA target sites suggests that they can effectively inhibit translation. Genome Res. 23, 604-615. https://doi.org/10.1101/gr.139758.112
  14. Hu, T., Pi, W., Zhu, X., Yu, M., Ha, H., Shi, H., Choi, J.H., and Tuan, D. (2017). Long non-coding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function. Nucleic Acids Res. 45, 4479-4492. https://doi.org/10.1093/nar/gkx055
  15. Inoue-Murayama, M., Adachi, S., Mishima, N., Mitani, H., Takenaka, O., Terao, K., Hayasaka, I., Ito, S., and Murayama, Y. (2002). Variation of variable number of tandem repeat sequences in the 3′-untranslated region of primate dopamine transporter genes that affects reporter gene expression. Neurosci. Lett. 334, 206-210. https://doi.org/10.1016/S0304-3940(02)01125-4
  16. Jash, A., Yun, K., Sahoo, A., So, J.S., and Im, S.H. (2012). Looping mediated interaction between the promoter and 3' UTR regulates type II collagen expression in chondrocytes. PLoS One 7, e40828. https://doi.org/10.1371/journal.pone.0040828
  17. Jia, X., Wang, F., Han, Y., Geng, X., Li, M., Shi, Y., Lu, L., and Chen, Y. (2016). miR-137 and miR-491 negatively regulate dopamine transporter expression and function in neural cells. Neurosci. Bull. 32, 512-522. https://doi.org/10.1007/s12264-016-0061-6
  18. Jung, Y.D., Lee, H.E., Jo, A., Hiroo, I., Cha, H.J., and Kim, H.S. (2017). Activity analysis of LTR12C as an effective regulatory element of the RAE1 gene. Gene 634, 22-28. https://doi.org/10.1016/j.gene.2017.08.037
  19. Kel, A.E., Gossling, E., Reuter, I., Cheremushkin, E., Kel-Margoulis, O.V., and Wingender, E. (2003). MATCH: a tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res. 31, 3576-3579. https://doi.org/10.1093/nar/gkg585
  20. Kim, V.N. (2005). MicroRNA biogenesis: coordinated cropping and dicing. Nat. Rev. Mol. Cell Biol. 6, 376-385. https://doi.org/10.1038/nrm1644
  21. Koressaar, T., Lepamets, M., Kaplinski, L., Raime, K., Andreson, R., and Remm, M. (2018). Primer3_masker: integrating masking of template sequence with primer design software. Bioinformatics 34, 1937-1938. https://doi.org/10.1093/bioinformatics/bty036
  22. Kozomara, A., Birgaoanu, M., and Griffiths-Jones, S. (2019). miRBase: from microRNA sequences to function. Nucleic Acids Res. 47, D155-D162.
  23. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., Devon, K., Dewar, K., Doyle, M., FitzHugh, W., et al. (2001). Initial sequencing and analysis of the human genome. Nature 409, 860-921. https://doi.org/10.1038/35057062
  24. Lee, H.E., Jo, A., Im, J., Cha, H.J., Kim, W.J., Kim, H.H., Kim, D.S., Kim, W., Yang, T.J., and Kim, H.S. (2019). Characterization of the long terminal repeat of the endogenous retrovirus-derived microRNAs in the olive flounder. Sci. Rep. 9, 14007. https://doi.org/10.1038/s41598-019-50492-7
  25. Lee, I., Ajay, S.S., Yook, J.I., Kim, H.S., Hong, S.H., Kim, N.H., Dhanasekaran, S.M., Chinnaiyan, A.M., and Athey, B.D. (2009). New class of microRNA targets containing simultaneous 5'-UTR and 3'-UTR interaction sites. Genome Res. 19, 1175-1183. https://doi.org/10.1101/gr.089367.108
  26. Li, G., Wu, X., Qian, W., Cai, H., Sun, X., Zhang, W., Tan, S., Wu, Z., Qian, P., Ding, K., et al. (2016). CCAR1 5' UTR as a natural miRancer of miR-1254 overrides tamoxifen resistance. Cell Res. 26, 655-673. https://doi.org/10.1038/cr.2016.32
  27. Liu, G., Zhang, R., Xu, J., Wu, C.I., and Lu, X. (2015). Functional conservation of both CDS- and 3'-UTR-located microRNA binding sites between species. Mol. Biol. Evol. 32, 623-628. https://doi.org/10.1093/molbev/msu323
  28. Marques, A.C., Tan, J., Lee, S., Kong, L., Heger, A., and Ponting, C.P. (2012). Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of mRNAs. Genome Biol. 13, R102. https://doi.org/10.1186/gb-2012-13-11-r102
  29. Nakamura, Y., Leppert, M., O'Connell, P., Wolff, R., Holm, T., Culver, M., Martin, C., Fujimoto, E., Hoff, M., Kumlin, E., et al. (1987). Variable number of tandem repeat (VNTR) markers for human gene mapping. Science 235, 1616-1622. https://doi.org/10.1126/science.3029872
  30. O'Brien, J., Hayder, H., Zayed, Y., and Peng, C. (2018). Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front. Endocrinol. (Lausanne) 9, 402. https://doi.org/10.3389/fendo.2018.00402
  31. Pacheco, A., Berger, R., Freedman, R., and Law, A.J. (2019). A VNTR regulates miR-137 expression through novel alternative splicing and contributes to risk for schizophrenia. Sci. Rep. 9, 11793. https://doi.org/10.1038/s41598-019-48141-0
  32. Petri, R., Brattas, P.L., Sharma, Y., Jonsson, M.E., Pircs, K., Bengzon, J., and Jakobsson, J. (2019). LINE-2 transposable elements are a source of functional human microRNAs and target sites. PLoS Genet. 15, e1008036. https://doi.org/10.1371/journal.pgen.1008036
  33. Piriyapongsa, J. and Jordan, I.K. (2007). A family of human microRNA genes from miniature inverted-repeat transposable elements. PLoS One 2, e203. https://doi.org/10.1371/journal.pone.0000203
  34. Piriyapongsa, J., Marino-Ramirez, L., and Jordan, I.K. (2007). Origin and evolution of human microRNAs from transposable elements. Genetics 176, 1323-1337. https://doi.org/10.1534/genetics.107.072553
  35. Qin, S., Jin, P., Zhou, X., Chen, L., and Ma, F. (2015). The role of transposable elements in the origin and evolution of microRNAs in human. PLoS One 10, e0131365. https://doi.org/10.1371/journal.pone.0131365
  36. Rehmsmeier, M., Steffen, P., Hochsmann, M., and Giegerich, R. (2004). Fast and effective prediction of microRNA/target duplexes. RNA 10, 1507-1517. https://doi.org/10.1261/rna.5248604
  37. Roberts, J.T., Cardin, S.E., and Borchert, G.M. (2014). Burgeoning evidence indicates that microRNAs were initially formed from transposable element sequences. Mob. Genet. Elements 4, e29255. https://doi.org/10.4161/mge.29255
  38. Sabino, F.C., Ribeiro, A.O., Tufik, S., Torres, L.B., Oliveira, J.A., Mello, L.E., Cavalcante, J.S., and Pedrazzoli, M. (2014). Evolutionary history of the PER3 variable number of tandem repeats (VNTR): idiosyncratic aspect of primate molecular circadian clock. PLoS One 9, e107198. https://doi.org/10.1371/journal.pone.0107198
  39. Salem, A.M., Ismail, S., Zarouk, W.A., Abdul Baky, O., Sayed, A.A., Abd El-Hamid, S., and Salem, S. (2013). Genetic variants of neurotransmitter-related genes and miRNAs in Egyptian autistic patients. ScientificWorldJournal 2013, 670621.
  40. Schmitz, L.J.M., Klaassen, R.V., Ruiperez-Alonso, M., Zamri, A.E., Stroeder, J., Rao-Ruiz, P., Lodder, J.C., van der Loo, R.J., Mansvelder, H.D., Smit, A.B., et al. (2017). The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory. Elife 6, e24192. https://doi.org/10.7554/elife.24192
  41. Shi, F., Zhang, Y., Wang, J., Su, J., Liu, Z., and Wang, T. (2019). RNAsequencing identified miR-3681 as a negative regulator in the proliferation and migration of cervical cancer cells via the posttranscriptional suppression of HGFR. RSC Adv. 9, 22376-22383. https://doi.org/10.1039/C9RA01785B
  42. Thompson, P.J., Macfarlan, T.S., and Lorincz, M.C. (2016). Long terminal repeats: from parasitic elements to building blocks of the transcriptional regulatory repertoire. Mol. Cell 62, 766-776. https://doi.org/10.1016/j.molcel.2016.03.029
  43. Vaira, V., Roncoroni, L., Barisani, D., Gaudioso, G., Bosari, S., Bulfamante, G., Doneda, L., Conte, D., Tomba, C., Bardella, M.T., et al. (2014). microRNA profiles in coeliac patients distinguish different clinical phenotypes and are modulated by gliadin peptides in primary duodenal fibroblasts. Clin. Sci. (Lond). 126, 417-423. https://doi.org/10.1042/CS20130248
  44. Vaz, C., Ahmad, H.M., Sharma, P., Gupta, R., Kumar, L., Kulshreshtha, R., and Bhattacharya, A. (2010). Analysis of microRNA transcriptome by deep sequencing of small RNA libraries of peripheral blood. BMC Genomics 11, 288. https://doi.org/10.1186/1471-2164-11-288
  45. Wicker, T., Sabot, F., Hua-Van, A., Bennetzen, J.L., Capy, P., Chalhoub, B., Flavell, A., Leroy, P., Morgante, M., Panaud, O., et al. (2007). A unified classification system for eukaryotic transposable elements. Nat. Rev. Genet. 8, 973-982. https://doi.org/10.1038/nrg2165
  46. Wingender, E., Chen, X., Fricke, E., Geffers, R., Hehl, R., Liebich, I., Krull, M., Matys, V., Michael, H., Ohnhauser, R., et al. (2001). The TRANSFAC system on gene expression regulation. Nucleic Acids Res. 29, 281-283. https://doi.org/10.1093/nar/29.1.281
  47. Yamamura, S., Imai-Sumida, M., Tanaka, Y., and Dahiya, R. (2018). Interaction and cross-talk between non-coding RNAs. Cell. Mol. Life Sci. 75, 467-484. https://doi.org/10.1007/s00018-017-2626-6