Homeotic miRNAs: From Development to Pathologies

  • Maya Ameyar-Zazoua
  • Irina Naguibneva
  • Linda Pritchard
  • Annick Harel-Bellan

Abstract Hox genes are key elements for anterio-posterior morphogenesis. Hox genes are tightly regulated at the transcriptional level. This level of regulation, however, is by far not unique, and non-coding RNAs, and in particular micro-RNAs, provide an important supplementary level of regulation. This review recapitulates what is known about Hox-related microRNAs, describes a technique that can be used to address miRNA function and attempts to speculate on the function of regulation by miRNAs and how it may impact on medicine.

Keywords

miRNA Hox LNA 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bernstein, E., Kim, S.Y., Carmell, M.A., Murchison, E.P., Alcorn, H., Li, M.Z., Mills, A.A., Elledge, S.J., Anderson, K.V., and Hannon, G.J. (2003). Dicer is essential for mouse develop-ment. Nat Genet 35, 215-217. CrossRefPubMedGoogle Scholar
  2. 2.
    Brend, T., Gilthorpe, J., Summerbell, D., and Rigby, P.W. (2003). Multiple levels of transcrip-tional and post-transcriptional regulation are required to define the domain of Hoxb4 expression. Development 130, 2717-2728.CrossRefPubMedGoogle Scholar
  3. 3.
    Cuellar, T.L., and McManus, M.T. (2005). MicroRNAs and endocrine biology. J Endocrinol 187, 327-332.CrossRefPubMedGoogle Scholar
  4. 4.
    Cullen, B.R. (2004). Transcription and processing of human microRNA precursors. Mol Cell 16, 861-865.CrossRefPubMedGoogle Scholar
  5. 5.
    Deschamps, J., van den Akker, E., Forlani, S., De Graaff, W., Oosterveen, T., Roelen, B., and Roelfsema, J. (1999). Initiation, establishment and maintenance of Hox gene expression pat-terns in the mouse. Int J Dev Biol 43, 635-650.PubMedGoogle Scholar
  6. 6.
    Duboule, D. (1991). Patterning in the vertebrate limb. Curr Opin Genet Dev 1, 211-216.CrossRefPubMedGoogle Scholar
  7. 7.
    Filipowicz, W., Bhattacharyya, S.N., and Sonenberg, N. (2008). Mechanisms of post-tran-scriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9, 102-114.CrossRefPubMedGoogle Scholar
  8. 8.
    Forlani, S., Lawson, K.A., and Deschamps, J. (2003). Acquisition of Hox codes during gas-trulation and axial elongation in the mouse embryo. Development 130, 3807-3819.CrossRefPubMedGoogle Scholar
  9. 9.
    Fuchtbauer, E.M. (1995). Expression of M-twist during postimplantation development of the mouse. Dev Dyn 204, 316-322.PubMedGoogle Scholar
  10. 10.
    Fujimura, Y., Isono, K., Vidal, M., Endoh, M., Kajita, H., Mizutani-Koseki, Y., Takihara, Y., van Lohuizen, M., Otte, A., Jenuwein, T., et al. (2006). Distinct roles of Polycomb group gene products in transcriptionally repressed and active domains of Hoxb8. Development 133, 2371-2381.CrossRefPubMedGoogle Scholar
  11. 11.
    Hagan, J.P., and Croce, C.M. (2007). MicroRNAs in carcinogenesis. Cytogen Genome Res 118, 252-259.CrossRefGoogle Scholar
  12. 12.
    Hakem, A., Sanchez-Sweatman, O., You-Ten, A., Duncan, G., Wakeham, A., Khokha, R., and Mak, T.W. (2005). RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis. Genes Dev 19, 1974-1979.CrossRefPubMedGoogle Scholar
  13. 13.
    Harfe, B.D., McManus, M.T., Mansfield, J.H., Hornstein, E., and Tabin, C.J. (2005). The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci USA 102, 10898-10903.CrossRefPubMedGoogle Scholar
  14. 14.
    Hornstein, E., Mansfield, J.H., Yekta, S., Hu, J.K., Harfe, B.D., McManus, M.T., Baskerville, S., Bartel, D.P., and Tabin, C.J. (2005). The microRNA miR-196 acts upstream of Hoxb8 and shh in limb development. Nature 438, 671-674.CrossRefPubMedGoogle Scholar
  15. 15.
    Hutvagner, G., and Simard, M.J. (2008). Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol 9, 22-32.CrossRefPubMedGoogle Scholar
  16. 16.
    Iimura, T., and Pourquie, O. (2007). Hox genes in time and space during vertebrate body for-mation. Dev Growth Differ 49, 265-275.PubMedGoogle Scholar
  17. 17.
    . Jackson, R.J., and Standart, N. (2007). How do microRNAs regulate gene expression? Sci STKE 2007, re1.Google Scholar
  18. 18.
    Kanellopoulou, C., Muljo, S.A., Kung, A.L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D.M., and Rajewsky, K. (2005). Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19, 489-501.CrossRefPubMedGoogle Scholar
  19. 19.
    Koshkin, A.A., Nielsen, P., Meldgaard, M., Rajwanshi, V. K., Singh, S. K., and Wengel, J (1998). LNA (Locked Nucleic Acid): an RNA mimic forming exceedingly stable LNA:LNA duplexes. J Am Chem Soc 120, 13252-13260.CrossRefGoogle Scholar
  20. 20.
    Ma, L., Teruya-Feldstein, J., and Weinberg, R.A. (2007). Tumour invasion and metastasis initi-ated by microRNA-10b in breast cancer. Nature 449, 682-688.CrossRefPubMedGoogle Scholar
  21. 21.
    Mansfield, J.H., Harfe, B.D., Nissen, R., Obenauer, J., Srineel, J., Chaudhuri, A., Farzan-Kashani, R., Zuker, M., Pasquinelli, A.E., Ruvkun, G., et al. (2004). MicroRNA-responsive ‘sensor’ transgenes uncover Hox-like and other developmentally regulated patterns of verte-brate microRNA expression. Nat Genet 36, 1079-1083.CrossRefPubMedGoogle Scholar
  22. 22.
    Meister, G., Landthaler, M., Dorsett, Y., and Tuschl, T. (2004). Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA 10, 544-550.CrossRefPubMedGoogle Scholar
  23. 23.
    Moss, E.G., Lee, R.C., and Ambros, V. (1997). The cold shock domain protein LIN-28 con-trols developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88, 637-646. CrossRefPubMedGoogle Scholar
  24. 24.
    Muljo, S.A., Ansel, K.M., Kanellopoulou, C., Livingston, D.M., Rao, A., and Rajewsky, K. (2005). Aberrant T cell differentiation in the absence of Dicer. J Exp Med 202, 261-269.CrossRefPubMedGoogle Scholar
  25. 25.
    Naguibneva, I., Ameyar-Zazoua, M., Nonne, N., Polesskaya, A., Ait-Si-Ali, S., Groisman, R., Souidi, M., Pritchard, L.L., and Harel-Bellan, A. (2006a). An LNA-based loss-of-function assay for micro-RNAs. Biomed Pharmacother 60(9), 633-638.CrossRefGoogle Scholar
  26. 26.
    Naguibneva, I., Ameyar-Zazoua, M., Polesskaya, A., Ait-Si-Ali, S., Groisman, R., Souidi, M., Cuvellier, S., and Harel-Bellan, A. (2006b). The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol 8, 278-284.CrossRefGoogle Scholar
  27. 27.
    Nelson, C.E., Morgan, B.A., Burke, A.C., Laufer, E., DiMambro, E., Murtaugh, L.C., Gonzales, E., Tessarollo, L., Parada, L.F., and Tabin, C. (1996). Analysis of Hox gene expres-sion in the chick limb bud. Development 122, 1449-1466.PubMedGoogle Scholar
  28. 28.
    O’Rourke, M.P., and Tam, P.P. (2002). Twist functions in mouse development. Int J Dev Biol 46, 401-413.PubMedGoogle Scholar
  29. 29.
    Oosterveen, T., Niederreither, K., Dolle, P., Chambon, P., Meijlink, F., and Deschamps, J. (2003). Retinoids regulate the anterior expression boundaries of 5′ Hoxb genes in posterior hindbrain. Embo J 22, 262-269.CrossRefPubMedGoogle Scholar
  30. 30.
    Pearson, J.C., Lemons, D., and McGinnis, W. (2005). Modulating Hox gene functions during animal body patterning. Nat Rev Genet 6, 893-904.CrossRefPubMedGoogle Scholar
  31. 31.
    Ronshaugen, M., Biemar, F., Piel, J., Levine, M., and Lai, E.C. (2005). The Drosophila micro-RNA iab-4 causes a dominant homeotic transformation of halteres to wings. Genes Dev 19, 2947-2952.CrossRefPubMedGoogle Scholar
  32. 32.
    Thiery, J.P., and Morgan, M. (2004). Breast cancer progression with a Twist. Nat Med 10, 777-778.CrossRefPubMedGoogle Scholar
  33. 33.
    Woltering, J.M., and Durston, A.J. (2008). MiR-10 Represses HoxB1a and HoxB3a in Zebrafish. PLoS ONE 3, e1396.CrossRefPubMedGoogle Scholar
  34. 34.
    Yamamoto, M., and Kuroiwa, A. (2003). Hoxa-11 and Hoxa-13 are involved in repression of MyoD during limb muscle development. Dev Growth Differ 45, 485-498.CrossRefPubMedGoogle Scholar
  35. 35.
    Yang, J., Mani, S.A., Donaher, J.L., Ramaswamy, S., Itzykson, R.A., Come, C., Savagner, P., Gitelman, I., Richardson, A., and Weinberg, R.A. (2004). Twist, a master regulator of mor-phogenesis, plays an essential role in tumor metastasis. Cell 117, 927-939.CrossRefPubMedGoogle Scholar
  36. 36.
    Yekta, S., Shih, I.H., and Bartel, D.P. (2004). MicroRNA-directed cleavage of HOXB8 mRNA. Science 304, 594-596.CrossRefPubMedGoogle Scholar
  37. 37.
    Zhao, Y., Ransom, J.F., Li, A., Vedantham, V., von Drehle, M., Muth, A.N., Tsuchihashi, T., McManus, M.T., Schwartz, R.J., and Srivastava, D. (2007). Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129, 303-317.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media B.V 2008

Authors and Affiliations

  • Maya Ameyar-Zazoua
    • 1
  • Irina Naguibneva
    • 1
  • Linda Pritchard
    • 1
  • Annick Harel-Bellan
    • 1
  1. 1.Centre National de la Recherche Scientifique (CNRS) FRE 2944, Institut André Lwoff, Villejuif F-94801France; Université Paris-SudVillejuifFrance

Personalised recommendations