Regulation of the mRNA-binding Protein AUF1 by Activation of the β -Adrenergic Receptor Signal Transduction Pathway

Pende, Aldo; Tremmel, Kelli D.; DeMaria, Christine T.; Blaxall, Burns C.; Minobe, Wayne; Sherman, Jonathan A.; Bisognano, John D.; Bristow, Michael R.; Brewer, Gary; Port, J. David

doi:10.1074/jbc.271.14.8493

Cited by 150 publications

(134 citation statements)

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“…This could possibly lead to an interchange of mRNA binding proteins, a mechanism which may provide an e cient way of regulating mRNA degradation. In view of experiments performed in vitro (DeMaria and Ma et al, 1996) or with cell cultures (Buzby et al, 1996;Ma et al, 1996;Pende et al, 1996;Sirenko et al, 1997), we could postulate that their binding contributes to mRNA decay. We thus expected to ®nd an inverse relationship between their expression levels and those of c-myc transcripts.…”

Section: Discussionmentioning

confidence: 99%

Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins

et al. 1998

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Several proteins that may regulate c-myc mRNA posttranscriptionally were previously isolated and characterized. Two of them, HuR and AUF1, bind speci®cally to the 3' untranslated region (UTR) of c-myc mRNA. Because c-myc is regulated post-transcriptionally in various mouse tissues, including quiescent tissues, fetal liver and regenerating liver, we investigated whether HuR and AUF1 expression was also regulated in these tissues. Concerning AUF1, we analysed the expression of various mRNA and protein isoforms. We discovered a new AUF1 mRNA variant with a long AU-rich 3' UTR. We show that AUF1 expression, regardless of the RNA isoform considered, and HuR mRNA expression parallel c-myc expression in quiescent tissues and during liver development; their expression is high in lymphoid tissues and fetal liver and low in adult liver. However, no upregulation of HuR or AUF1 accompanies the upregulation of c-myc mRNA following partial hepatectomy. We discuss our results in relation to the current hypothesis that HuR and AUF1 act as mRNA destabilizing factors.

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Section: Discussionmentioning

confidence: 99%

Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins

et al. 1998

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“…An additional AU-binding factor, AUF1, is a M r 37,000 protein purified and cloned from the cytoplasmic extract of human leukemia cells (32). Although AUF1 has been shown to bind to ␤ 2 AR mRNA via the 3Ј-UTR, its nonidentity with ␤ARB protein was established by immunoprecipitation and immunoblotting analyses of AUF1 polypeptides of UV cross-linking products (52). DeMaria and Brewer (53) demonstrated that AUF1-ARE binding affinity is directly related to the potency with which an ARE destabilizes a heterologous mRNA.…”

Section: Discussionmentioning

confidence: 99%

A 20-Nucleotide (A + U)-rich Element of β2-Adrenergic Receptor (β2AR) mRNA Mediates Binding to β2AR-binding Protein and Is Obligate for Agonist-induced Destabilization of Receptor mRNA

Tholanikunnel

Malbon

1997

Journal of Biological Chemistry

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The M r 35,000 ␤-adrenergic receptor mRNA-binding protein, termed ␤ARB protein, is induced by ␤-adrenergic agonists and binds to ␤ 2 -receptor mRNAs that display agonist-induced destabilization. A cognate sequence in the mRNA was identified previously that provides for ␤ARB protein binding in vitro. In the present work, the sequence established in vitro for binding of ␤ARB protein to hamster ␤ 2 -adrenergic receptor mRNA was probed in vivo by site-directed mutagenesis of the 3-untranslated region and expression in Chinese hamster ovary cells. Agonist-induced down-regulation of G protein-linked receptors, such as the ␤ 2 -adrenergic receptor, provides an explanation for long term adaptation to chronic stimuli characteristically observed for members of this receptor family (1-5). For ␤ 2 -adrenergic receptors, steady-state levels of the receptor and its mRNA decline following a challenge with agonist (2, 3). The basis for the decline in receptor mRNA induced by agonist is not transcriptional suppression, but rather post-transcriptional destabilization of receptor mRNAs (6). Recently, we identified a M r 35,000 protein with properties consistent with those expected for an RNA-binding protein selective for mRNAs of receptors that display agonist-induced down-regulation of their messages and protein expression. This M r 35,000 ␤-adrenergic receptor mRNA-binding protein, termed ␤ARB 1 protein (7), demonstrates several RNA binding properties (8) similar to (A ϩ U)-rich element (ARE)-binding proteins reported by others (9 -12).The steady-state levels of highly regulated mRNAs (e.g. mRNAs of granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-␣, and the oncogenes c-myc and c-fos) are markedly influenced by the rate of degradation (13-20). Regulation of mRNA stability and turnover is multifaceted, reflecting not only various cytosolic and nuclear-associated factors and polyadenylation, but also cognate sequences of the 3Ј-untranslated regions (UTR) of mRNA, such as the tandem repeats of AUUUA pentamers (9 -12, 21-23) and nonamers, such as UUAUUUA(U/A)(U/A) (24) and UUAUUUAUU (25).Several classes of RNA-binding proteins have been implicated in regulating mRNA stability and turnover. The heterogeneous, nuclear ribonucleoprotein particles participate in several steps of mRNA maturation including packaging, translocation, and splicing of heterogenous nuclear RNA (26 -28). Splicing and further processing of pre-mRNAs possessing introns, a 5Ј-cap and 3Ј-poly(A) ϩ tract involves the small nuclear RNA-binding proteins (29,30). Cytosolic mRNA-binding proteins include the M r 72,000 poly(A)-binding protein, which binds to long stretches (ϳ25 nucleotides/protein) of poly(A) ϩ and stabilizes the RNA to 3Ј-to 5Ј-nuclease activity (31). A subset of smaller (ranging from M r 30,000 to 40,000), cytosolic mRNA-binding proteins have been identified that display recognition of AU-rich domains in the 3Ј-UTR (7, 9 -12, 32, 33). Although several of these proteins have been purified (32,33), the precise role that these small...

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“…In conclusion, the efficiency of ARE-dependent mRNA turnover is compromised in cells containing low levels of endogenous p37 AUF1 and p40 AUF1 (Ross et al, 1991;Buzby et al, 1996) or following sequestration of AUF1 by treatment with hemin (Loflin et al, 1999). Conversely, in congestive heart failure, an increase in AUF1 protein levels accompanies a lower expression of b 1 -adrenergic receptor mRNA, possibly mediated by an ARE-related mechanism (Pende et al, 1996(Pende et al, ,1999.…”

Section: Auf1mentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

290

259

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Recent evidence suggests that gene expression may be regulated, at least in part, at post-transcriptional level by factors inducing the extremely rapid degradation of messenger RNAs. These factors include reactions between adenyl-uridyl-rich elements (AREs) of the relevant mRNA and either specific proteins that bind to these elements or exosomes. This review deals with examples of the proteins (AU-rich binding proteins, AUBPs) and exosomes, which have been shown to form complexes with AREs and bring about rapid degradation of the relevant mRNA, and with certain other factors, which protect the RNA from such degradation. The biochemical and physiological factors underlying the stability of messenger RNAs carrying the ARE motifs will be reviewed in the light of their emerging significance for cell physiology, human pathology, and molecular medicine. We also consider the possible application of the results of recent insights into the mechanisms to pharmacological interventions to prevent or cure disorders, especially developmental disorders, which the suppression of gene expression may bring about. Molecular targeting of specific steps in protein degradation by synthetic compounds has already been utilized for the development of pharmacological therapies.

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Regulation of the mRNA-binding Protein AUF1 by Activation of the β -Adrenergic Receptor Signal Transduction Pathway

Cited by 150 publications

References 63 publications

Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins

Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins

A 20-Nucleotide (A + U)-rich Element of β2-Adrenergic Receptor (β2AR) mRNA Mediates Binding to β2AR-binding Protein and Is Obligate for Agonist-induced Destabilization of Receptor mRNA

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

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