Synchronous and regulated expression of two AU-binding proteins, AUF1 and HuR, throughout murine development

Gouble, Agnès; Morello, Dominique

doi:10.1038/sj.onc.1203910

Cited by 43 publications

(36 citation statements)

References 55 publications

(51 reference statements)

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“…One level of regulation is that of the abundance of the mRNA binding proteins themselves. To this end, the functional, intracellular concentrations of HuR and AUF1 are regulated by multiple factors including external stimuli, the cell cycle, and pathophysiological processes such as cellular hypertrophy or hyperplasia (Pende et al 1996;Lafon et al 1998;Blaxall et al 2000a;Gouble and Morello 2000;Wang et al 2000a). A second level of regulation is that of the intracellular localization of the mRNA binding protein and/ or the mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…Under unstimulated conditions, HuR is primarily localized to the nucleus, but its movement to the cytoplasm has been associated with stabilization of mRNA transcripts (Atasoy et al 1998;Fan and Steitz 1998a,b). HuR itself has also been shown to be regulated at the protein level (MartinezChantar et al 2006), with changes in expression correlating with a growth phenotype (Blaxall et al 2000a;Gouble and Morello 2000) and with changes in phosphorylation affecting localization and function (Abdelmohsen et al 2007;Doller et al 2007). In contrast to HuR, a number of other proteins, e.g., TTP, KSRP, and BRF1, confer instability to ARE-containing mRNAs (Taylor and Blackshear 1995;Taylor et al 1996;Carballo et al 2000;Ming et al 2001;Stoecklin et al 2002;Gherzi et al 2004;Lu and Schneider 2004;Raineri et al 2004;Schmidlin et al 2004;Linker et al 2005;Ogilvie et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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FRET-detectable interactions between the ARE binding proteins, HuR and p37AUF1

David¹,

Tanveer²,

Port³

2007

RNA

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A number of highly regulated gene classes are regulated post-transcriptionally at the level of mRNA stability. A central feature in these mRNAs is the presence of A+U-rich elements (ARE) within their 39 UTRs. Two ARE binding proteins, HuR and AUF1, are associated with mRNA stabilization and destabilization, respectively. Previous studies have demonstrated homomultimerization of each protein and the capacity to bind simultaneous or competitively to a single ARE. To investigate this possibility further, cell biological and biophysical approaches were undertaken. Protein-protein interaction was monitored by fluorescence resonance energy transfer (FRET) and by immunocytochemistry in live and fixed cells using fluorescently labeled CFP/YFP fusion proteins of HuR and p37AUF1. Strong nuclear FRET between HuR/HuR and AUF1/AUF1 homodimers as well as HuR/AUF1 heterodimers was observed. Treatment with the MAP kinase activator, anisomycin, which commonly stabilizes ARE-containing mRNAs, caused rapid nuclear to cytoplasmic shuttling of HuR. AUF1 also underwent shuttling, but on a longer time scale. After shuttling, HuR/HuR, AUF1/AUF1, and HuR/AUF1, FRET was also observed in the cytoplasm. In further studies, arsenite rapidly induced the formation of stress granules containing HuR and TIA-1 but not AUF1. The current studies demonstrate that two mRNA binding proteins, HuR and AUF1, are colocalized and are capable of functional interaction in both the nucleus and cytoplasm. FRET-based detection of AUF1/HuR interaction may serve as a basis of opening up new dimensions in delineating the functional interaction of mRNA binding proteins with RNA turnover.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FRET-detectable interactions between the ARE binding proteins, HuR and p37AUF1

David¹,

Tanveer²,

Port³

2007

RNA

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“…A number of proteins that selectively bind AREs have been identified and characterized. ARE-binding regulators of mRNA stability include: AUF1 (heterogeneous nuclear ribonucleoprotein (hnRNP-D), four members of the ELAV family [HuR (human)/HuA (murine), HuB/Hel-N1, HuC, HUD], glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), hnRNPA1, hnRNPC, and tristeraprolin (TTP) (15,16). We have shown that of those RNA binding proteins, AUF1, HuR (HuA-like), and TTP are expressed in MC3T3-E1 cells (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

p38 MAPK Regulates IL‐1β Induced IL‐6 Expression Through mRNA Stability in Osteoblasts

Patil

Zhu

Rossa

et al. 2004

Immunological Investigations

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Osteoblast-derived IL-6 functions in coupled bone turnover by supporting osteoclastogenesis favoring bone resorption instead of bone deposition. Gene regulation of IL-6 is complex occurring both at transcription and post-transcription levels. The focus of this paper is at the level of mRNA stability, which is important in IL-6 gene regulation. Using the MC3T3-E1 as an osteoblastic model, IL-6 secretion was dose dependently decreased by SB203580, a p38 MAPK inhibitor. Steady state IL-6 mRNA was decreased with SB203580 (2μM) ca. 85% when stimulated by IL-1β (1 5ng/ml). These effects require de novo protein synthesis as they were inhibited by cycloheximide. p38 MAPK had minor effects on proximal IL-6 promoter activity in reporter gene assays. A more significant effect on IL-6 mRNA stability was observed in the presence of SB203580. Western blot analysis confirmed that SB203580 inhibited p38 MAP kinase, in response to IL-1β in a dose dependent manner in MC3T3-E1 cells. Stably transfected MC3T3-E1 reporter cell lines (MC6) containing green fluorescent protein (GFP) with the 3′ untranslated region of IL-6 was constructed. Results indicated that IL-1β, TNFα, LPS but not parathyroid hormone (PTH) could increase GFP expression of these reporter cell lines. Endogenous IL-6 and reporter gene eGFP-IL-6 3′ UTR mRNA was regulated by p38 in MC6 cells. In addition, transient transfection of IL-6 3′ UTR reporter cells with immediate upstream MAP kinase kinase-3 and -6 increased GFP expression compared to mock transfected controls. These results indicate that p38 MAPK regulates IL-1β-stimulated IL-6 at a post transcriptional mechanism and one of the primary targets of IL-6 gene regulation is the 3′ UTR of IL-6.

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“…One study analyzed the spatial-temporal expression of HuR and AUF1 mRNAs and proteins during development of mice (Gouble and Morello, 2000). HuR and AUF1 expression differed considerably among tissues and at different developmental stages.…”

Section: Regulation Of Are-binding Proteinsmentioning

confidence: 99%

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

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

293

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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Synchronous and regulated expression of two AU-binding proteins, AUF1 and HuR, throughout murine development

Cited by 43 publications

References 55 publications

FRET-detectable interactions between the ARE binding proteins, HuR and p37AUF1

FRET-detectable interactions between the ARE binding proteins, HuR and p37AUF1

p38 MAPK Regulates IL‐1β Induced IL‐6 Expression Through mRNA Stability in Osteoblasts

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

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