Cytoplasmic Fate of Eukaryotic mRNA: Identification and Characterization of AU-Binding Proteins

Jarzembowski, Jason A.; Malter, James S.

doi:10.1007/978-3-642-60471-3_7

Cited by 20 publications

(17 citation statements)

References 120 publications

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“…The transfected cell type (A) and the presence or absence of the FGF-2 5Ј-leader (B) are indicated on top of each panel. (23). In fact, sequence comparison revealed homology of the FGF-2 DEST element to the interleukin-2 and vascular endothelial growth factor AREs, which are also unusual (29,30).…”

Section: Fig 2 Expression and Half-lives Of Transfected Cat Mrnasmentioning

confidence: 99%

“…However, each of these repeats contained only a single AUUUA motif (Fig. 4A), whereas AREs described in proto-oncogene and lymphokine mRNAs always contain reiterated AUUUA motifs (23).…”

Section: Fig 1 Rt-pcr Quantification Of Different Fgf-2 Mrna 3-utrsmentioning

confidence: 99%

“…The ARE-mediated destabilization mechanism, although still mechanistically unclear, involves RNA/protein interactions. At least 10 ARE-specific binding proteins have been identified to date, with different affinities for specific RNA sequences (23). Nine of them are able to bind to the c-myc ARE, and six of them are able to bind to poly(U); two of these proteins, AU-B and AU-C, are unable to bind to the c-myc ARE or poly(U).…”

Section: Fig 2 Expression and Half-lives Of Transfected Cat Mrnasmentioning

confidence: 99%

“…23). The stability of most of these mRNAs is regulated by AU-rich elements (AREs) present in the 3Ј-UTR (23).…”

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confidence: 99%

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Expression of Human Fibroblast Growth Factor 2 mRNA Is Post-transcriptionally Controlled by a Unique Destabilizing Element Present in the 3′-Untranslated Region between Alternative Polyadenylation Sites

Touriol

Morillon

Gensac

et al. 1999

Journal of Biological Chemistry

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Fibroblast growth factor 2 (FGF-2) belongs to a family of 18 genes coding for either mitogenic differentiating factors or oncogenic proteins, the expression of which must be tightly controlled. We looked for regulatory elements in the 5823-nucleotide-long 3-untranslated region of the FGF-2 mRNA that contains eight potential alternative polyadenylation sites. Quantitative reverse transcription-polymerase chain reaction revealed that poly(A) site utilization was cell type-dependent, with the eighth poly(A) site being used (95%) in primary human skin fibroblasts, whereas proximal sites were used in the transformed cell lines studied here. We used a cell transfection approach with synthetic reporter mRNAs to localize a destabilizing element between the first and second poly(A) sites. Although AU-rich, the FGF-2-destabilizing element had unique features: it involved a 122-nucleotide direct repeat, with both elements of the repeat being required for the destabilizing activity. These data show that short stable FGF-2 mRNAs are present in transformed cells, whereas skin fibroblasts contain mostly long unstable mRNAs, suggesting that FGF-2 mRNA stability cannot be regulated in transformed cells. The results also provide evidence of a multilevel post-transcriptional control of FGF-2 expression; such a stringent control prevents FGF-2 overexpression and permits its expression to be enhanced only in relevant physiological situations.

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Section: Fig 2 Expression and Half-lives Of Transfected Cat Mrnasmentioning

confidence: 99%

“…However, each of these repeats contained only a single AUUUA motif (Fig. 4A), whereas AREs described in proto-oncogene and lymphokine mRNAs always contain reiterated AUUUA motifs (23).…”

Section: Fig 1 Rt-pcr Quantification Of Different Fgf-2 Mrna 3-utrsmentioning

confidence: 99%

Section: Fig 2 Expression and Half-lives Of Transfected Cat Mrnasmentioning

confidence: 99%

“…23). The stability of most of these mRNAs is regulated by AU-rich elements (AREs) present in the 3Ј-UTR (23).…”

mentioning

confidence: 99%

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Expression of Human Fibroblast Growth Factor 2 mRNA Is Post-transcriptionally Controlled by a Unique Destabilizing Element Present in the 3′-Untranslated Region between Alternative Polyadenylation Sites

Touriol

Morillon

Gensac

et al. 1999

Journal of Biological Chemistry

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“…This suggests that the surrounding context or secondary structure is also important for recognition of the ARE of MFA2 by regulatory factors. Several ARE-binding factors have been identified both in mammalian and yeast systems, but it remains unclear how binding of these proteins leads to modulation of mRNA decay rates (22,27,49).A number of studies have implicated the Hsp70 (heat shock protein 70) family of chaperone proteins in regulating decay of ARE-containing transcripts in mammalian systems (19,26,52,57). The Hsp70 family comprises highly conserved, essential ATP-binding proteins involved in diverse cellular functions during both stress and nonstress conditions (24,31,39).…”

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confidence: 99%

A Yeast Homologue of Hsp70, Ssa1p, Regulates Turnover of the MFA2 Transcript through Its AU-Rich 3′ Untranslated Region

Duttagupta

Vasudevan

Wilusz

et al. 2003

Molecular and Cellular Biology

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Many eukaryotic mRNAs exhibit regulated decay in response to cellular signals. AU-rich elements (AREs) identified in the 3 untranslated region (3-UTR) of several such mRNAs play a critical role in controlling the half-lives of these transcripts. The yeast ARE-containing mRNA, MFA2, has been studied extensively and is degraded by a deadenylation-dependent mechanism. However, the trans-acting factors that promote the rapid decay of MFA2 have not been identified. Our results suggest that the chaperone protein Hsp70, encoded by the SSA family of genes, is involved in modulating MFA2 mRNA decay. MFA2 is specifically stabilized in a strain bearing a temperature-sensitive mutation in the SSA1 gene. Furthermore, an AU-rich region within the 3-UTR of the message is both necessary and sufficient to confer this regulation. Stabilization occurs as a result of slower deadenylation in the ssa1 ts strain, suggesting that Hsp70 is required for activation of the turnover pathway.Gene expression is a highly controlled process involving regulation at both transcriptional and posttranscriptional levels. In recent years mRNA turnover has emerged as an important target for the regulation of gene expression (33,54). A large number of mRNAs encoding cytokines, growth factors, and proto-oncogenes display regulated decay in response to external signals (44, 50). Hence, understanding the pathways regulating transcript stability is of critical importance. Selective mRNA degradation is mediated by a number of different cisacting sequences, including the most-investigated class, called AU-rich elements (AREs), present in the 3Ј untranslated region (3Ј-UTR) of a variety of mammalian and yeast mRNAs (44,49,54). Recent experiments have shown that the pathways and factors involved in ARE-mediated mRNA decay are conserved between yeast and higher eukaryotes, making yeast an ideal system for the study of this phenomenon (49).The ARE is a stability determinant whose sequence is loosely defined and ranges in size from 50 to 150 nucleotides. These elements are typically found in the 3Ј-UTR and contain one or more copies of the pentameric sequence AUUUA flanked by a high content of U's and A's (8, 47). An important feature of many AREs is that they modulate the stability of transcripts in response to cellular stimuli. They can cause instability under some conditions by enhancing the rate of removal of the poly(A) tail and the subsequent degradation of the body of the transcript (7, 38, 48). In contrast, under stabilizing conditions AREs can inhibit the decay process (see references 49 and 54 and references therein). In yeast, at least two classes of ARE-containing mRNAs have been identified, represented by the MFA2 and TIF51A/HYP2 transcripts (49). In both cases decay proceeds through poly(A) tail shortening followed by decapping and 5Ј33Ј exonucleolytic decay (36, 49). The stability of the TIF51A transcript is modulated in response to changes in carbon source (11,49). The mRNA is stable in cells grown in glucose and unstable in cells grown under nong...

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Understanding the Translation Regulatory Mechanisms to Improve the Efficiency and the Specificity of Protein Production by the Cell Factory

et al. 1999

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Cytoplasmic Fate of Eukaryotic mRNA: Identification and Characterization of AU-Binding Proteins

Cited by 20 publications

References 120 publications

Expression of Human Fibroblast Growth Factor 2 mRNA Is Post-transcriptionally Controlled by a Unique Destabilizing Element Present in the 3′-Untranslated Region between Alternative Polyadenylation Sites

Expression of Human Fibroblast Growth Factor 2 mRNA Is Post-transcriptionally Controlled by a Unique Destabilizing Element Present in the 3′-Untranslated Region between Alternative Polyadenylation Sites

A Yeast Homologue of Hsp70, Ssa1p, Regulates Turnover of the MFA2 Transcript through Its AU-Rich 3′ Untranslated Region

Understanding the Translation Regulatory Mechanisms to Improve the Efficiency and the Specificity of Protein Production by the Cell Factory

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