Engagement of Tumor Necrosis Factor mRNA by an Endotoxin-Inducible Cytoplasmic Protein

Gueydan, Cyril; Houzet, Laurent; Marchant, Arnaud; Sels, André; Huez, Georges; Kruys, Véronique

doi:10.1007/bf03401907

Cited by 24 publications

(32 citation statements)

References 30 publications

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“…The exact contribution of these processes will require further studies to measure transcriptional activity using nuclear run-on assays and to assess the course of mRNA degradation. The 3Ј-UTR of the TNF-␣ gene confers a similar translational repressive effect on TNF-␣ mRNA (27,50). Interestingly, although the translational repression caused by the TNF-␣ 3Ј-UTR is relieved by LPS (this study and Refs.…”

Section: Discusssionsupporting

confidence: 50%

“…In brief, four fragments of cDNA corresponding to AU1 (ϩ727 to ϩ818), AU2 (ϩ807 to ϩ936), AU3 (ϩ1157 to ϩ1239), and AU4 (ϩ727 to ϩ1239) regions of the 3Ј-UTR of IL-10 mRNA were cloned into an XbaI site (ϩ1934) located between the luciferase gene and the poly(A) signal in the pGL3-control vector carrying a SV40 promoter/luciferase expression unit. A construct containing the 3Ј-UTR of the TNF-␣ cDNA inserted into the XbaI site of the pGL3-control vector was provided by Dr. C. Gueydan (Free University, Brussels, Belgium) (27).…”

Section: Dna Constructsmentioning

confidence: 99%

“…To study the regulation of IL-10 production by adenosine, we used RAW 264.7 macrophages; these cells have been shown to express adenosine receptors (20,27,28,33), and many aspects of the regulation of IL-10 gene expression have been uncovered using this cell line (6,7,13). RAW 264.7 macrophages produce constitutively low levels of IL-10.…”

Section: Adenosine Receptor Agonists Up-regulate Il-10 Production By mentioning

confidence: 99%

“…The reporter construct that we used carried cDNA corresponding to the entire 3Ј-UTR of the TNF-␣ mRNA, which was inserted into the XbaI site of the pGL3-control vector (27). In accord with results of previous studies using this (27,49) and other similar (50) constructs, we found that LPS induced a large increase in reporter activity (Fig. 6A), which was far greater (ϳ20-fold) than that achieved by using the empty pGL3-control vector (ϳ30% increase; Fig.…”

Section: Adenosine Receptor Activation Does Not Affect Tnf 3ј-utr Funmentioning

confidence: 99%

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Adenosine Augments IL-10 Production by Macrophages through an A2B Receptor-Mediated Posttranscriptional Mechanism

Németh¹,

Lutz²,

Csóka³

et al. 2005

The Journal of Immunology

244

161

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Adenosine receptor ligands have anti-inflammatory effects and modulate immune responses by up-regulating IL-10 production by immunostimulated macrophages. The adenosine receptor family comprises G protein-coupled heptahelical transmembrane receptors classified into four types: A1, A2A, A2B, and A3. Our understanding of the signaling mechanisms leading to enhanced IL-10 production following adenosine receptor occupancy on macrophages is limited. In this study, we demonstrate that adenosine receptor occupancy increases IL-10 production by LPS-stimulated macrophages without affecting IL-10 promoter activity and IL-10 mRNA levels, indicating a posttranscriptional mechanism. Transfection experiments with reporter constructs containing sequences corresponding to the AU-rich 3′-untranslated region (UTR) of IL-10 mRNA confirmed that adenosine receptor activation acts by relieving the translational repressive effect of the IL-10 3′-UTR. By contrast, adenosine receptor activation failed to liberate the translational arrest conferred by the 3′-UTR of TNF-α mRNA. The IL-10 3′-UTR formed specific complexes with proteins present in cytoplasmic extracts of RAW 264.7 cells. Adenosine enhanced binding of proteins to a region of the IL-10 3′-UTR containing the GUAUUUAUU nonamer. The stimulatory effect of adenosine on IL-10 production was mediated through the A2B receptor, because the order of potency of selective agonists was 5′-N-ethylcarboxamidoadenosine (NECA) > N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA) > 2-chloro-N6-cyclopentyladenosine (CCPA) = 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethyl-carboxamidoadenosine (CGS-21680). Also, the selective A2B antagonist, alloxazine, prevented the effect of adenosine. Collectively, these studies identify a novel pathway in which activation of a G protein-coupled receptor augments translation of an anti-inflammatory gene.

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Section: Discusssionsupporting

confidence: 50%

Section: Dna Constructsmentioning

confidence: 99%

Section: Adenosine Receptor Agonists Up-regulate Il-10 Production By mentioning

confidence: 99%

Section: Adenosine Receptor Activation Does Not Affect Tnf 3ј-utr Funmentioning

confidence: 99%

See 2 more Smart Citations

Adenosine Augments IL-10 Production by Macrophages through an A2B Receptor-Mediated Posttranscriptional Mechanism

Németh¹,

Lutz²,

Csóka³

et al. 2005

The Journal of Immunology

244

161

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“…Indeed, AUR sequences have been demonstrated to reduce the stability of mRNA (16), but in some cases AUR sequences inhibit translation without affecting the mRNA stability (15). Proteins can interact with AUR sequences (2,19,24,42), and some of these protein-AUR complexes can either increase mRNA stability (27) or decrease their translational efficiency (10,46).In erythroblasts, inhibitory proteins have been purified and demonstrated to interact with oligonucleotide repeats present in the 3ЈUTR of the lipoxygenase mRNA (25).We have previously shown that alternative polyadenylation of amyloid precursor protein (APP) mRNA generates two sets of transcripts which differ by the length of their 3ЈUTR and by their translational efficiency (5). The 258 nucleotides (nt) located within the two utilized polyadenylation sites are clearly involved in the modulation of translation.…”

mentioning

confidence: 99%

A GG Nucleotide Sequence of the 3′ Untranslated Region of Amyloid Precursor Protein mRNA Plays a Key Role in the Regulation of Translation and the Binding of Proteins

Mbella

Bertrand

Huez

et al. 2000

Molecular and Cellular Biology

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The alternative polyadenylation of the mRNA encoding the amyloid precursor protein (APP) involved in Alzheimer's disease generates two molecules, with the first of these containing 258 additional nucleotides in the 3 untranslated region (3 UTR). We have previously shown that these 258 nucleotides increase the translation of APP mRNA injected in Xenopus oocytes (5). Here, we demonstrate that this mechanism occurs in CHO cells as well. We also present evidence that the 3 UTR containing 8 nucleotides more than the short 3 UTR allows the recovery of an efficiency of translation similar to that of the long 3 UTR. Moreover, the two guanine residues located at the 3 ends of these 8 nucleotides play a key role in the translational control. Using gel retardation mobility shift assay, we show that proteins from Xenopus oocytes, CHO cells, and human brain specifically bind to the short 3 UTR but not to the long one. The two guanine residues involved in the translational control inhibit this specific binding by 65%. These results indicate that there is a correlation between the binding of proteins to the 3 UTR of APP mRNA and the efficiency of mRNA translation, and that a GG motif controls both binding of proteins and translation.The control of gene expression governs cell differentiation. The first step of this control is provided by the transcription of specific genes. In eucaryotic cells, the scanning of a gene by the RNA polymerase II leads to the production of a nuclear transcript which, in most cases, will undergo three major modifications: capping of its 5Ј untranslated region (5ЈUTR), polyadenylation of the 3ЈUTR, and splicing of introns (13,38).At the postranscriptional level, the efficiency of translation of mature mRNA can also regulate gene expression. The phosphorylation of initiation factors of translation, which interact with the 5Ј end of mRNAs, has been demonstrated to modulate translation (21, 31).The presence of secondary structures in the 5ЈUTR can also influence mRNA translation either by increasing the binding affinity of some eucaryotic initiation factors (18) or by interacting with cellular proteins which can completely inhibit the initiation of translation (9,33).Although the 3ЈUTR is located downstream of the coding sequence, it has been widely demonstrated that this region can also modulate mRNA translation (41). The poly(A) tail is one element of the 3ЈUTR implicated in both the stability of mRNA and the regulation of its translation (34). The poly(A) tail can increase the stability of an mRNA molecule by protecting the mRNA from digestion by 3Ј35Ј exonucleases (7). A more dynamic role has been attributed to the poly(A) tail since it was demonstrated that its removal from the 3Ј end of capped mRNA decreases translation (22, 37). In Saccharomyces cerevisiae the enhancement of translation mediated by the poly(A) tail requires the formation of a complex between the poly(A) tail and a poly(A) binding protein (PABP) since the depletion of the PABP results in the inhibition of translation (36). This co...

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MICROFILAMENT‐DEPENDENT MODULATION OF CYTOPLASMIC PROTEIN BINDING TO TNFα mRNA AU‐RICH INSTABILITY ELEMENT IN HUMAN LYMPHOID CELLS

Henics

1999

Cell Biology International

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Cytoplasmic proteins with binding capability to AU-rich instability determinant sequences (ARE) of tumour necrosis factor alpha (TNFalpha) mRNA 3' untranslated region (3'UTR) were assessed in human lymphoid cells. In vitro label transfer experiments using wild type as well as mutant sequences in which the 70 nucleotide-long AUUUA pentamer-containing portion of the 3'UTR had been deleted conferred binding specificity to five major activities of 22/25-, 38/40-, 50-, 60- and 80-kDa proteins in cytoplasmic extracts of peripheral blood mononuclear cells (PBMCs). Cytochalasin-induced disarrangement of the F-actin-based microfilament system led to a Triton X-100-insoluble to soluble redistribution of these binding activities. No such changes were observed in Jurkat tumour cells. Combination of in vivo UV-crosslinking and in vitro label transfer experiments revealed considerable differences in RNA association between proteins of the same cell type as well as between proteins of identical molecular weight (Mw) derived from either PBMCs or Jurkat cells. Our findings may explain some aspects of differential regulation of interleukin 2 (IL-2) and TNFalpha mRNA stability upon microfilament disruption in human PBMCs observed in an earlier study. These results also suggest that the physical state of cytoplasmic structural environment might contribute to important regulatory processes regarding key elements of eukaryotic mRNA metabolism, such as modulation of stability. Finally, these data highlight the possibility that the often observed disorganization of the cytoskeleton in tumour cells may partly be responsible for the maintenance of the neoplastic state, a phenomenon that potentially involves ARE-AUBP interactions.

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Engagement of Tumor Necrosis Factor mRNA by an Endotoxin-Inducible Cytoplasmic Protein

Cited by 24 publications

References 30 publications

Adenosine Augments IL-10 Production by Macrophages through an A2B Receptor-Mediated Posttranscriptional Mechanism

Adenosine Augments IL-10 Production by Macrophages through an A2B Receptor-Mediated Posttranscriptional Mechanism

A GG Nucleotide Sequence of the 3′ Untranslated Region of Amyloid Precursor Protein mRNA Plays a Key Role in the Regulation of Translation and the Binding of Proteins

MICROFILAMENT‐DEPENDENT MODULATION OF CYTOPLASMIC PROTEIN BINDING TO TNFα mRNA AU‐RICH INSTABILITY ELEMENT IN HUMAN LYMPHOID CELLS

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