Translation and Transcription: the Dual Functionality of LysRS in Mast Cells

  • Yannay-Cohen, Nurit (Department of Biochemistry, Hebrew University Hadassah Medical School) ;
  • Razin, Ehud (Department of Biochemistry, Hebrew University Hadassah Medical School)
  • Received : 2006.05.08
  • Accepted : 2006.05.10
  • Published : 2006.10.31

Abstract

In the post genome project era, it is well established that the human genome contains a smaller number of genes than expected. The complexity found in higher organisms can be explained if proteins are multifunctional. Indeed, recent studies are continuing to reveal proteins that are capable of a broad repertoire of functions. A good paradigm for multifunctionality can be found in the amino-acyl tRNA synthetases (aaRSs), an ancient conserved family of proteins. This unique family, which is comprised of 20 different enzymes, is well known for its participation in protein synthesis. Several studies have described numerous examples of these "housekeeping" proteins taking part in extensive critical cellular activities. In this review, we focus on a member of that family, lysyl-tRNA synthetase (LysRS), which has been shown to have a dual functionality. In addition to its contribution to the translation process, LysRS also takes part in the regulation of MITF and USF2 target genes. This phenomenon was first described in mast cells.

Keywords

Acknowledgement

Supported by : United States Binational Science Foundation, the Israeli Academy of Science, GermanIsraeli Foundation for Scientific Research and Development, Korean and the Israeli ministries of science

References

  1. Asai, K., Kitaura, J., Kawakami, Y., Yamagata, N., Tsai, M., et al. (2001) Regulation of mast cell survival by IgE. Immunity 14, 791-800 https://doi.org/10.1016/S1074-7613(01)00157-1
  2. Barnes, L. D., Garrison, P. N., Siprashvili, Z., Guranowski, A., Robinson, A. K., et al. (1996) Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5'''-P1,P3-triphosphate hydrolase. Biochemistry 35, 11529-11535 https://doi.org/10.1021/bi961415t
  3. Bessman, M. J., Frick, D. N., and O'Handley, S. F. (1996) The MutT proteins or 'Nudix' hydrolases, a family of versatile, widely distributed, 'housecleaning' enzymes. J. Biol. Chem. 271, 25059-25062 https://doi.org/10.1074/jbc.271.41.25059
  4. Blanquet, S., Plateau, P., and Brevet, A. (1983) The role of zinc in 5',5'-diadenosine tetraphosphate production by aminoacyltransfer RNA synthetases. Mol. Cell. Biochem. 52, 3-11
  5. Brenner, C. (2002) Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. Biochemistry 41, 9003-9014 https://doi.org/10.1021/bi025942q
  6. Brenner, C., Garrison, P., Gilmour, J., Peisach, D., Ringe, D., et al. (1997) Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins. Nat. Struct. Biol. 4, 231-238. https://doi.org/10.1038/nsb0397-231
  7. Brenner, C., Cadiou, H., Vieira, H. L., Zamzami, N., Marzo, I., et al. (2000) Bcl-2 and Bax regulate the channel activity of the mitochondrial adenine nucleotide translocator. Oncogene 19, 329-336 https://doi.org/10.1038/sj.onc.1203298
  8. Brevet, A., Plateau, P., Cirakoglu, B., Pailliez, J. P., and Blanquet, S. (1982) Zinc-dependent synthesis of 5',5'-diadenosine tetraphosphate by sheep liver lysyl- and phenylalanyl-tRNA synthetases. J. Biol. Chem. 257, 14613-14615
  9. Brevet, A., Chen, J., Leveque, F., Plateau, P., and Blanquet, S. (1989) In vivo synthesis of adenylylated bis(5'-nucleosidyl) tetraphosphates (Ap4N) by Escherichia coli aminoacyl-tRNA synthetases. Proc. Natl. Acad. Sci. USA 86, 8275-8279
  10. Coussens, L. M., Raymond, W. W., Bergers, G., Laig-Webster, M., Behrendtsen, O., et al. (1999) Inflammatory mast cells upregulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev. 13, 1382-1397 https://doi.org/10.1101/gad.13.11.1382
  11. Echtenacher, B., Mannel, D. N., and Hultner, L. (1996) Critical protective role of mast cells in a model of acute septic peritonitis. Nature 381, 75-77 https://doi.org/10.1038/381075a0
  12. Galli, S. J., Maurer, M., and Lantz, C. S. (1999) Mast cells as sentinels of innate immunity. Curr. Opin. Immunol. 11, 53-59 https://doi.org/10.1016/S0952-7915(99)80010-7
  13. Hadsell, D. L., Bonnette, S., George, J., Torres, D., Klementidis, Y., et al. (2003) Diminished milk synthesis in upstream stimulatory factor 2 null mice is associated with decreased circulating oxytocin and decreased mammary gland expression of eukaryotic initiation factors 4E and 4G. Mol. Endocrinol. 17, 2251-2267 https://doi.org/10.1210/me.2002-0031
  14. Hara, M., Ono, K., Hwang, M. W., Iwasaki, A., Okada, M., et al. (2002) Evidence for a role of mast cells in the evolution to congestive heart failure. J. Exp. Med. 195, 375-381 https://doi.org/10.1084/jem.20002036
  15. Hodgkinson, C. A., Moore, K. J., Nakayama, A., Steingrimsson, E., Copeland, N. G. J., et al. (1993) Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 74, 395-404 https://doi.org/10.1016/0092-8674(93)90429-T
  16. Ibba, M. and Soll, D. (2001) The renaissance of aminoacyl-tRNA synthesis. EMBO Rep. 2, 382-387 https://doi.org/10.1093/embo-reports/kve095
  17. Isozaki, K., Tsujimura, T., Nomura, S., Morii, E., Koshimizu, U., et al. (1994) Cell type-specific deficiency of c-kit gene expression in mutant mice of mi/mi genotype. Am. J. Pathol. 145, 827-836
  18. Ito, A., Morii, E., Maeyama, K., Jippo, T., Kim, D. K., et al. (1998) Systematic method to obtain novel genes that are regulated by mi transcription factor: impaired expression of granzyme B and tryptophan hydroxylase in mi/mi cultured mast cells. Blood 91, 3210-3221
  19. Ito, A., Morii, E., Kim, D. K., Kataoka, T. R., Jippo, T., et al. (1999) Inhibitory effect of the transcription factor encoded by the mi mutant allele in cultured mast cells of mice. Blood 93, 1189-1196
  20. Jakubowski, H. (1983) Synthesis of diadenosine 5',5'''-P1,P4- tetraphosphate and related compounds by plant (Lupinus luteus) seryl-tRNA and phenylalanyl-tRNA synthetases. Acta Biochim. Pol. 30, 51-69
  21. Ji, L., Fang, B., Yen, N., Fong, K., Minna, J. D., et al. (1999) Induction of apoptosis and inhibition of tumorigenicity and tumor growth by adenovirus vector-mediated fragile histidine triad (FHIT) gene overexpression. Cancer Res. 59, 3333-3339
  22. Kalesnikoff, J., Huber, M., Lam, V., Damen, J. E., Zhang, J., et al. (2001) Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity 14, 801-811 https://doi.org/10.1016/S1074-7613(01)00159-5
  23. Kim, J. Y., Kang, Y. S., Lee, J. W., Kim, H. J., Ahn, Y. H., et al. (2002) p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: implications for its physiological significance. Proc. Natl. Acad. Sci. USA 99, 7912-7916
  24. Kitamura, Y., Morii, E., Jippo, T., and Ito, A. (2002) Effect of MITF on mast cell differentiation. Mol. Immunol. 38, 1173- 1176 https://doi.org/10.1016/S0161-5890(02)00058-5
  25. Lantz, C. S., Boesiger, J., Song, C. H., Mach, N., Kobayashi, T., et al. (1998) Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392, 90-93 https://doi.org/10.1038/32190
  26. Lee, Y. N. and Razin, E. (2005) Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcepsilonRI-activated mast cells. Mol. Cell. Biol. 25, 8904-8912 https://doi.org/10.1128/MCB.25.20.8904-8912.2005
  27. Lee, Y. N., Nechushtan, H., Figov, N., and Razin, E. (2004) The function of Lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells. Immunity 20, 145-151 https://doi.org/10.1016/S1074-7613(04)00020-2
  28. Leitges, M., Gimborn, K., Elis, W., Kalesnikoff, J., Hughes, M. R., et al. (2002) Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation. Mol. Cell. Biol. 22, 3970-3980 https://doi.org/10.1128/MCB.22.12.3970-3980.2002
  29. Lemaitre, J. M., Buckle, R. S., and Mechali, M. (1996) c-Myc in the control of cell proliferation and embryonic development. Adv. Cancer Res. 70, 95-144 https://doi.org/10.1016/S0065-230X(08)60873-8
  30. Lima, C. D., Klein, M. G., and Hendrickson, W. A. (1997) Structure- based analysis of catalysis and substrate definition in the HIT protein family. Science 278, 286-290 https://doi.org/10.1126/science.278.5336.286
  31. Luo, X. and Sawadogo, M. (1996) Antiproliferative properties of the USF family of helix-loop-helix transcription factors. Proc. Natl. Acad. Sci. USA 93, 1308-1313
  32. Malaviya, R., Ikeda, T., Ross, E., and Abraham, S. N. (1996) Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature 381, 77-80 https://doi.org/10.1038/381077a0
  33. Matsuda, H., Watanabe, N., Kiso, Y., Hirota, S., Ushio, H., et al. (1990) Necessity of IgE antibodies and mast cells for manifestation of resistance against larval Haemaphysalis longicornis ticks in mice. J. Immunol. 144, 259-262
  34. McGill, G. G., Horstmann M., Widlund H. R., Du, J., Motyckova, G., et al. (2002) Bc12 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 109, 707-718 https://doi.org/10.1016/S0092-8674(02)00762-6
  35. Merkulova, T., Kovaleva, G., and Kisselev, L. (1994) P1,P3- bis(5'-adenosyl)triphosphate (Ap3A) as a substrate and a product of mammalian tryptophanyl-tRNA synthetase. FEBS Lett. 350, 287-290 https://doi.org/10.1016/0014-5793(94)00764-0
  36. Morii, E., Jippo, T., Hashimoto, K., Kim, D.-K., Lee, Y.-M., et al. (1997) Abnormal expression of mouse mast cell protease 5 gene in cultured mast cells derived from mutant mi/mi mice. Blood 90, 3057-3066
  37. Morii, E., Tsujimura, T., Jippo, T., Hashimoto, K., Takebayashi, K., et al. (1996) Regulation of mouse mast cell protease 6 gene expression by transcription factor encoded by the mi locus. Blood 88, 2488-2494
  38. Nechushtan, H. and Razin, E. (1998) Deciphering the earlyresponse transcription factor networks in mast cells. Immunol. Today 19, 441-444 https://doi.org/10.1016/S0167-5699(98)01316-4
  39. Plateau, P. and Blanquet, S. (1982) Zinc-dependent synthesis of various dinucleoside 5',5'''-P1,P3-Tri- or 5'',5'''-P1,P4-tetraphosphates by Escherichia coli lysyl-tRNA synthetase. Biochemistry 21, 5273-5279 https://doi.org/10.1021/bi00264a024
  40. Plateau, P., Mayaux, J. F., and Blanquet, S. (1981) Zinc(II)- dependent synthesis of diadenosine 5',5'''-P(1),P(4)-tetraphosphate by Escherichia coli and yeast phenylalanyl transfer ribonucleic acid synthetases. Biochemistry 20, 4654-4662 https://doi.org/10.1021/bi00519a021
  41. Quevillon, S. and Mirande, M. (1996) The p18 component of the multisynthetase complex shares a protein motif with the beta and gamma subunits of eukaryotic elongation factor 1. FEBS Lett. 395, 63-67 https://doi.org/10.1016/0014-5793(96)01005-8
  42. Quevillon, S., Agou, F., Robinson, J. C., and Mirande, M. (1997) The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyteactivating polypeptide II cytokine. J. Biol. Chem. 272, 32573- 32579 https://doi.org/10.1074/jbc.272.51.32573
  43. Quevillon, S., Robinson, J. C., Berthonneau, E., Siatecka, M., and Mirande, M. (1999) Macromolecular assemblage of aminoacyl- tRNA synthetases: identification of protein-protein interactions and characterization of a core protein. J. Mol. Biol. 285, 183-195 https://doi.org/10.1006/jmbi.1998.2316
  44. Rapaport, E. and Zamecnik, P. C. (1976) Presence of diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) in mamalian cells in levels varying widely with proliferative activity of the tissue: a possible positive 'pleiotypic activator'. Proc. Natl. Acad. Sci. USA 73, 3984-3988
  45. Razin, E., Zhang, Z. C., Nechushtan, H., Frenkel, S., Lee, Y. N., et al. (1999) Suppression of microphthalmia transcriptional activity by its association with protein kinase C-interacting protein 1 in mast cells. J. Biol. Chem. 274, 34272-34276 https://doi.org/10.1074/jbc.274.48.34272
  46. Robinson, J. C., Kerjan, P., and Mirande, M. (2000) Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly. J. Mol. Biol. 304, 983-994 https://doi.org/10.1006/jmbi.2000.4242
  47. Sampath, P., Mazumder, B., Seshadri, V., Gerber, C. A., Chavatte, L., et al. (2004) Noncanonical function of glutamyl-prolyltRNA synthetase: gene-specific silencing of translation. Cell 119, 195-208 https://doi.org/10.1016/j.cell.2004.09.030
  48. Secor, V. H., Secor, W. E., Gutekunst, C. A., and Brown, M. A. (2000) Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis. J. Exp. Med. 191, 813-822 https://doi.org/10.1084/jem.191.5.813
  49. Siprashvili, Z., Sozzi, G., Barnes, L. D., McCue, P., Robinson, A. K., et al. (1997) Replacement of Fhit in cancer cells suppresses tumorigenicity. Proc. Natl. Acad. Sci. USA 94, 13771-13776
  50. Sirito, M., Lin, Q., Deng, J. M., Behringer, R. R., and Sawadogo, M. (1998) Overlapping roles and asymmetrical crossregulation of the USF proteins in mice. Proc. Natl. Acad. Sci. USA 95, 3758-3763
  51. Stechschulte, D. J., Sharma, R., Dileepan, K. N., Simpson, K. M., Aggarwal, N., et al. (1987) Effect of the mi allele on mast cells, basophils, natural killer cells, and osteoclasts in C57Bl/6J mice. J. Cell Physiol. 132, 565-570 https://doi.org/10.1002/jcp.1041320321
  52. Stevens, J. and Loutit, J. F. (1982) Mast cells in spotted mutant mice (W Ph mi). Proc. R Soc. Lond B Biol. Sci. 215, 405-409
  53. Su, T., Suzui, M., Wang, L., Lin, C. S., Xing, W. Q., et al. (2003) Deletion of histidine triad nucleotide-binding protein 1/PKCinteracting protein in mice enhances cell growth and carcinogenesis. Proc. Natl. Acad. Sci USA 100, 7824-7829
  54. Vallet, V. S., Casado, M., Henrion, A. A., Bucchini, D., Raymondjean, M., et al. (1998) Differential roles of upstream stimulatory factors 1 and 2 in the transcriptional response of liver genes to glucose. J. Biol. Chem. 273, 20175-20179 https://doi.org/10.1074/jbc.273.32.20175
  55. Vartanian, A., Alexandrov, I., Prudowski, I., McLennan, A., and Kisselev, L. (1999) Ap4A induces apoptosis in human cultured cells. FEBS Lett. 456, 175-180 https://doi.org/10.1016/S0014-5793(99)00956-4
  56. Vartanian, A., Prudovsky, I., Suzuki, H., Dal Pra, I., and Kisselev, L. (1997) Opposite effects of cell differentiation and apoptosis on Ap3A/Ap4A ratio in human cell cultures. FEBS Lett. 415, 160-162 https://doi.org/10.1016/S0014-5793(97)01086-7
  57. Wahab, S. Z. and Yang, D. C. (1985) Influence of supramolecular structure on the enzyme mechanisms of rat liver lysyl-tRNA synthetase-catalyzed reactions. Synthesis of P1,P4-bis(5'- adenosyl)tetraphosphate. J. Biol. Chem. 260, 12735-12739
  58. Yamaguchi, M., Lantz, C. S., Oettgen, H. C., Katona, I. M., Fleming, T., et al. (1997) IgE enhances mouse mast cell Fc(epsilon) RI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions. J. Exp. Med. 185, 663-672 https://doi.org/10.1084/jem.185.4.663
  59. Zamecnik, P. C. (1969) An historical account of protein synthesis, with current overtones--a personalized view. Cold Spring Harb. Symp. Quant. Biol. 34, 1-16
  60. Zamecnik, P. C., Stephenson, M. L., Janeway, C. M., and Randerath, K. (1966) Enzymatic synthesis of diadenosine tetraphosphate and diadenosine triphosphate with a purified lysyl-sRNA synthetase. Biochem. Biophys. Res. Commun. 24, 91-97 https://doi.org/10.1016/0006-291X(66)90415-3