Characterization of the RNA Binding Proteins Forming Complexes with a Novel Putative Regulatory Region in the 3'-UTR of TNF-alpha MRNA

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 1998 May 21

PMID 9592171

Citations 13

Authors

Z Hel

S Di Marco

D Radzioch

Affiliations

Soon will be listed here.

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine regulator of an early immune response and the central mediator of deleterious effects of systemic inflammatory response syndrome. High production of TNF-alpha by macrophages requires two signals: the first signal induces transcription, while the second signal releases the translational repression of TNF-alpha mRNA. The translational control of TNF-alpha expression is conferred by sequences in the 3'-untranslated region (3'-UTR) of its mRNA. Previously, we have characterized protein complexes binding to the main AU-rich region in the 3'-UTR of murine TNF-alpha mRNA. Here we describe a second protein binding region which is located 147 bases downstream of the first region and interacts with at least seven distinct protein species present in murine macrophages. The second protein binding motif contains a single AUAUUUAU sequence motif; a mutation of this sequence to AUAGGUAU abrogates the binding of proteins. Some of the macrophage proteins mutually compete for the binding to both regions, while others seem to be region specific. The existence of the two protein binding domains explains the previously published data addressing the translatibility of a reporter gene linked to various deletion mutants of the TNF-alpha 3'-UTR. Both the sequence and position of the two putative protein binding regions are highly conserved across species, indicating their important role in the regulation of translational repression and inducibility of TNF-alpha synthesis.

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References

Laird-Offringa I, Elfferich P, Van Der Eb A . Rapid c-myc mRNA degradation does not require (A + U)-rich sequences or complete translation of the mRNA. Nucleic Acids Res. 1991; 19(9):2387-94. PMC: 329447. DOI: 10.1093/nar/19.9.2387. View

Beutler B, Brown T . A CAT reporter construct allows ultrasensitive estimation of TNF synthesis, and suggests that the TNF gene has been silenced in non-macrophage cell lines. J Clin Invest. 1991; 87(4):1336-44. PMC: 295168. DOI: 10.1172/JCI115137. View

Han J, Beutler B . The essential role of the UA-rich sequence in endotoxin-induced cachectin/TNF synthesis. Eur Cytokine Netw. 1990; 1(2):71-5. View

Han J, Beutler B, Huez G . Complex regulation of tumor necrosis factor mRNA turnover in lipopolysaccharide-activated macrophages. Biochim Biophys Acta. 1991; 1090(1):22-8. DOI: 10.1016/0167-4781(91)90032-h. View

Iwai Y, Bickel M, PLUZNIK D, Cohen R . Identification of sequences within the murine granulocyte-macrophage colony-stimulating factor mRNA 3'-untranslated region that mediate mRNA stabilization induced by mitogen treatment of EL-4 thymoma cells. J Biol Chem. 1991; 266(27):17959-65. View

Camussi G, Albano E, Tetta C, Bussolino F . The molecular action of tumor necrosis factor-alpha. Eur J Biochem. 1991; 202(1):3-14. DOI: 10.1111/j.1432-1033.1991.tb16337.x. View

Gurevich V, Pokrovskaya I, Obukhova T, Zozulya S . Preparative in vitro mRNA synthesis using SP6 and T7 RNA polymerases. Anal Biochem. 1991; 195(2):207-13. DOI: 10.1016/0003-2697(91)90318-n. View

Bohjanen P, Petryniak B, June C, Thompson C, LINDSTEN T . AU RNA-binding factors differ in their binding specificities and affinities. J Biol Chem. 1992; 267(9):6302-9. View

Suter P, Suter S, Girardin E, Roux-Lombard P, Grau G, Dayer J . High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis. 1992; 145(5):1016-22. DOI: 10.1164/ajrccm/145.5.1016. View

10.

Vassalli P . The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992; 10:411-52. DOI: 10.1146/annurev.iy.10.040192.002211. View

11.

Standiford T, Strieter R . TNF and IL-1 in sepsis: good cytokines gone bad. J Lab Clin Med. 1992; 120(2):179-80. View

12.

Muller W, Slor H, Pfeifer K, Huhn P, Bek A, Orsulic S . Association of AUUUA-binding protein with A+U-rich mRNA during nucleo-cytoplasmic transport. J Mol Biol. 1992; 226(3):721-33. DOI: 10.1016/0022-2836(92)90628-w. View

13.

Schiavi S, Belasco J, Greenberg M . Regulation of proto-oncogene mRNA stability. Biochim Biophys Acta. 1992; 1114(2-3):95-106. DOI: 10.1016/0304-419x(92)90009-n. View

14.

Dokter W, Sierdsema S, Esselink M, HALIE M, Vellenga E . IL-7 enhances the expression of IL-3 and granulocyte-macrophage-CSF mRNA in activated human T cells by post-transcriptional mechanisms. J Immunol. 1993; 150(7):2584-90. View

15.

Giroir B . Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade. Crit Care Med. 1993; 21(5):780-9. View

16.

Strieter R, Kunkel S, Bone R . Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med. 1993; 21(10 Suppl):S447-63. DOI: 10.1097/00003246-199310001-00006. View

17.

Zhang W, Wagner B, Ehrenman K, Schaefer A, DeMaria C, Crater D . Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1. Mol Cell Biol. 1993; 13(12):7652-65. PMC: 364837. DOI: 10.1128/mcb.13.12.7652-7665.1993. View

18.

Ulich T, Shin S, Del Castillo J . Haematologic effects of TNF. Res Immunol. 1993; 144(5):347-54. DOI: 10.1016/s0923-2494(93)80079-e. View

19.

Katz D, Theodorakis N, Cleveland D, LINDSTEN T, Thompson C . AU-A, an RNA-binding activity distinct from hnRNP A1, is selective for AUUUA repeats and shuttles between the nucleus and the cytoplasm. Nucleic Acids Res. 1994; 22(2):238-46. PMC: 307777. DOI: 10.1093/nar/22.2.238. View

20.

Lagnado C, Brown C, Goodall G . AUUUA is not sufficient to promote poly(A) shortening and degradation of an mRNA: the functional sequence within AU-rich elements may be UUAUUUA(U/A)(U/A). Mol Cell Biol. 1994; 14(12):7984-95. PMC: 359337. DOI: 10.1128/mcb.14.12.7984-7995.1994. View