Iron Regulation and the Cell Cycle
IDENTIFICATION OF AN IRON-RESPONSIVE ELEMENT IN THE 3 -UNTRANSLATED REGION OF HUMAN CELL DIVISION CYCLE 14A mRNA BY A REFINED MICROARRAY-BASED SCREENING STRATEGY *□
S
Received for publication, April 24, 2006, and in revised form, May 24, 2006 Published, JBC Papers in Press, June 7, 2006, DOI 10.1074/jbc.M603876200
Mayka Sanchez‡§, Bruno Galy‡, Thomas Dandekar¶, Peter Bengert¶ , Yevhen Vainshtein‡, Jens Stolte‡, Martina U. Muckenthaler§1, and Matthias W. Hentze‡2 From the ‡European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, the §Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, the ¶Department of Bioinformatics, Biozentrum, University of Wurzburg, Am Hubland, 97074 Wurzburg, and the Biochemistry Centre, ¨ ¨ University of Heidelberg, Im Neuenheimer Feld 365, 69120 Heidelberg, Germany
Iron regulatory proteins (IRPs) 1 and 2 post-transcriptionally control mammalian iron homeostasis by binding to iron-responsive elements (IREs), conserved RNA stem-loop structures located in the 5 - or 3 -untranslated regions of genes involved in iron metabolism (e.g. FTH1, FTL, and TFRC). To identify novel IRE-containing mRNAs, we integrated biochemical, biocomputational, and microarray-based experimental approaches. IRP/ IRE messenger ribonucleoproteins were immunoselected, and their mRNA composition was analyzed using an IronChip microarray enriched for genes predicted computationally to contain IRE-like motifs. Among different candidates, this report focuses on a novel IRE located in the 3 -untranslated region of the cell division cycle 14A mRNA. We
References: 1. Hentze, M. W., Muckenthaler, M. U., and Andrews, N. C. (2004) Cell 117, 285–297 2. Eisenstein, R. S., and Ross, K. L. (2003) J. Nutr. 133, 1510S–1516S 3. Schneider, B. D., and Leibold, E. A. (2000) Curr. Opin. Clin. Nutr. Metab. Care 3, 267–273 JOURNAL OF BIOLOGICAL CHEMISTRY 22873 IRE in CDC14A mRNA 4. Muckenthaler, M., Gray, N. K., and Hentze, M. W. (1998) Mol. Cell 2, 383–388 5. Galy, B., Ferring, D., and Hentze, M. W. (2005) Genesis 43, 181–188 6. Meyron-Holtz, E. G., Ghosh, M. C., Iwai, K., LaVaute, T., Brazzolotto, X., Berger, U. V., Land, W., Ollivierre-Wilson, H., Grinberg, A., Love, P., and Rouault, T. A. (2004) EMBO J. 23, 386 –395 7. Galy, B., Ferring, D., Minana, B., Bell, O., Janser, H. G., Muckenthaler, M., Schumann, K., and Hentze, M. W. (2005) Blood 106, 2580 –2589 8. LaVaute, T., Smith, S., Cooperman, S., Iwai, K., Land, W., Meyron-Holtz, E., Drake, S. K., Miller, G., Abu-Asab, M., Tsokos, M., Switzer, R., 3rd, Grinberg, A., Love, P., Tresser, N., and Rouault, T. A. (2001) Nat. Genet. 27, 209 –214 9. Smith, S. R., Ghosh, M. C., Ollivierre-Wilson, H., Hang Tong, W., and Rouault, T. A. (2006) Blood Cells Mol. Dis. 36, 283–287 10. Beaumont, C., Leneuve, P., Devaux, I., Scoazec, J. Y., Berthier, M., Loiseau, M. N., Grandchamp, B., and Bonneau, D. (1995) Nat. Genet. 11, 444 – 446 11. Kato, J., Fujikawa, K., Kanda, M., Fukuda, N., Sasaki, K., Takayama, T., Kobune, M., Takada, K., Takimoto, R., Hamada, H., Ikeda, T., and Niitsu, Y. (2001) Am. J. Hum. Genet. 69, 191–197 12. Hentze, M. W., Caughman, S. W., Casey, J. L., Koeller, D. M., Rouault, T. A., Harford, J. B., and Klausner, R. D. (1988) Gene (Amst.) 72, 201–208 13. Theil, E. C., and Eisenstein, R. S. (2000) J. Biol. Chem. 275, 40659 – 40662 14. Bengert, P., and Dandekar, T. (2003) Nucleic Acids Res. 31, 3441–3445 15. Dandekar, T., Stripecke, R., Gray, N. K., Goossen, B., Constable, A., Johansson, H. E., and Hentze, M. W. (1991) EMBO J. 10, 1903–1909 16. Gray, N. K., Pantopoulos, K., Dandekar, T., Ackrell, B. A., and Hentze, M. W. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 4925– 4930 17. Henderson, B. R., Menotti, E., Bonnard, C., and Kuhn, L. C. (1994) J. Biol. Chem. 269, 17481–17489 18. Butt, J., Kim, H. Y., Basilion, J. P., Cohen, S., Iwai, K., Philpott, C. C., Altschul, S., Klausner, R. D., and Rouault, T. A. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 4345– 4349 19. Meehan, H. A., and Connell, G. J. (2001) J. Biol. Chem. 276, 14791–14796 20. Muckenthaler, M., Richter, A., Gunkel, N., Riedel, D., PolycarpouSchwarz, M., Hentze, S., Falkenhahn, M., Stremmel, W., Ansorge, W., and Hentze, M. W. (2003) Blood 101, 3690 –3698 21. Gray, N. K., Quick, S., Goossen, B., Constable, A., Hirling, H., Kuhn, L. C., and Hentze, M. W. (1993) Eur. J. Biochem. 218, 657– 667 22. Church, G. M., and Gilbert, W. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 1991–1995 23. Mignone, F., Grillo, G., Licciulli, F., Iacono, M., Liuni, S., Kersey, P. J., Duarte, J., Saccone, C., and Pesole, G. (2005) Nucleic Acids Res. 33, D141–D146 24. Muckenthaler, M., Roy, C. N., Custodio, A. O., Minana, B., deGraaf, J., Montross, L. K., Andrews, N. C., and Hentze, M. W. (2003) Nat. Genet. 34, 102–107 25. Pfaffl, M. W. (2001) Nucleic Acids Res. 29, e45 26. Pantopoulos, K., and Hentze, M. W. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 1267–1271 27. Goossen, B., and Hentze, M. W. (1992) Mol. Cell. Biol. 12, 1959 –1966 28. Lymboussaki, A., Pignatti, E., Montosi, G., Garuti, C., Haile, D. J., and Pietrangelo, A. (2003) J. Hepatol. 39, 710 –715 29. Benes, V., and Muckenthaler, M. (2003) Trends Biochem. Sci. 28, 244 –249 30. Tchernitchko, D., Bourgeois, M., Martin, M. E., and Beaumont, C. (2002) Biochem. J. 363, 449 – 455 31. Binder, R., Horowitz, J. A., Basilion, J. P., Koeller, D. M., Klausner, R. D., and Harford, J. B. (1994) EMBO J. 13, 1969 –1980 32. Koeller, D. M., Casey, J. L., Hentze, M. W., Gerhardt, E. M., Chan, L. N., Klausner, R. D., and Harford, J. B. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 3574 –3578 33. Casey, J. L., Koeller, D. M., Ramin, V. C., Klausner, R. D., and Harford, J. B. (1989) EMBO J. 8, 3693–3699 34. Mullner, E. W., Neupert, B., and Kuhn, L. C. (1989) Cell 58, 373–382 35. Kohler, S. A., Menotti, E., and Kuhn, L. C. (1999) J. Biol. Chem. 274, 2401–2407 36. Cmejla, R., Petrak, J., and Cmejlova, J. (2006) Biochem. Biophys. Res. Commun. 341, 158 –166 37. Wong, A. K., Chen, Y., Lian, L., Ha, P. C., Petersen, K., Laity, K., Carillo, A., Emerson, M., Heichman, K., Gupte, J., Tavtigian, S. V., and Teng, D. H. (1999) Genomics 59, 248 –251 38. Kaiser, B. K., Zimmerman, Z. A., Charbonneau, H., and Jackson, P. K. (2002) Mol. Biol. Cell 13, 2289 –2300 39. Mailand, N., Lukas, C., Kaiser, B. K., Jackson, P. K., Bartek, J., and Lukas, J. (2002) Nat. Cell Biol. 4, 317–322 40. Hubert, N., and Hentze, M. W. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 12345–12350 41. Lam-Yuk-Tseung, S., and Gros, P. (2006) Biochemistry 45, 2294 –2301 42. Tabuchi, M., Tanaka, N., Nishida-Kitayama, J., Ohno, H., and Kishi, F. (2002) Mol. Biol. Cell 13, 4371– 4387 43. Farazi, T. A., Waksman, G., and Gordon, J. I. (2001) J. Biol. Chem. 276, 39501–39504 44. Gunshin, H., Allerson, C. R., Polycarpou-Schwarz, M., Rofts, A., Rogers, J. T., Kishi, F., Hentze, M. W., Rouault, T. A., Andrews, N. C., and Hediger, M. A. (2001) FEBS Lett. 509, 309 –316 45. Zoller, H., Theurl, I., Koch, R., Kaser, A., and Weiss, G. (2002) Blood Cells Mol. Dis. 29, 488 – 497 46. Paradkar, P. N., and Roth, J. A. (2006) Biochem. J. 394, 173–183 47. Lis, A., Paradkar, P. N., Singleton, S., Kuo, H. C., Garrick, M. D., and Roth, J. A. (2005) Biochem. Pharmacol. 69, 1647–1655 48. Wang, X., Garrick, M. D., Yang, F., Dailey, L. A., Piantadosi, C. A., and Ghio, A. J. (2005) Am. J. Physiol. 289, L24 –L33 49. Liang, S. X., and Richardson, D. R. (2003) Carcinogenesis 24, 1601–1614 50. Le, N. T., and Richardson, D. R. (2002) Biochim. Biophys. Acta 1603, 31– 46 Downloaded from www.jbc.org at Universitaet Heidelberg, on September 25, 2012 22874 JOURNAL OF BIOLOGICAL CHEMISTRY VOLUME 281 • NUMBER 32 • AUGUST 11, 2006