Developmental Regulation of RNA Transcript Destabilization by A + U-rich Elements is AUF1-dependent

Buzby, Jeffrey S.; Brewer, Gary; Nugent, Diane J.

doi:10.1074/jbc.274.48.33973

Cited by 59 publications

(53 citation statements)

References 65 publications

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“…Recently, Dixon et al (55) reported the importance of AREs in the post-transcriptional regulation of COX-2 mRNA. A number of ARE-binding proteins have been identified, including HuR (33), AUF1/heterogeneous nuclear ribonucleoprotein D (34,35), TIA-1 (36), and tristetraprolin (37). Binding of these proteins to AREs in the 3Ј-UTR can exert either positive or negative effects on stability, translation, and subcellular localization of the mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…These 3Ј-UTRs contain AU-rich elements (AREs) that are the binding sites for proteins that interact with the 3Ј-UTR to regulate mRNA deadenylation and decay (32), and the 3Ј-UTR of COX-2 contains many AREs. A number of ARE-binding proteins have been identified, including HuR (33), AUF1/heterogeneous nuclear ribonucleoprotein D (34,35), TIA-1 (36), and tristetraprolin (TTP) (37). Binding of some of these proteins to AREs in the 3Ј-UTR can enhance stability of the message, and HuR has been shown to stabilize COX-2 mRNA (38).…”

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confidence: 99%

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Tristetraprolin Binds to the 3′-Untranslated Region of Cyclooxygenase-2 mRNA

Sawaoka¹,

Dixon²,

Oates³

et al. 2003

Journal of Biological Chemistry

130

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In human colorectal adenocarcinoma cell lines, we found two major transcripts of cyclooxygenase-2, the full-length mRNA and a short polyadenylation variant (2577 kb) lacking the distal segment of the 3 -untranslated region. Tristetraprolin, an mRNA-binding protein that promotes message instability, was shown to bind the cyclooxygenase-2 mRNA in the region of the 3 -untranslated region between nucleotides 3125 and 3432 and to reduce levels of the full-length mRNA. During cell growth and confluence, the expression of tristetraprolin mRNA was inversely correlated with that of the fulllength cyclooxygenase-2 transcript, and transfection of tristetraprolin into HCA-7 cells reduced the level of fulllength cyclooxygenase-2 mRNA. However, the truncated transcript escaped tristetraprolin binding and downregulation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Tristetraprolin Binds to the 3′-Untranslated Region of Cyclooxygenase-2 mRNA

Sawaoka¹,

Dixon²,

Oates³

et al. 2003

Journal of Biological Chemistry

130

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“…[14][15][16][17][18][19][20][21] Rajagopalan and Malter 22 reported that mRNA containing the (AUGUA) Â 4 mutant sequence, the 3 0 UTR-truncated sequence or the normal/wild-type AUUUA sequence revealed dramatic differences in mRNA stability and polyribosome-binding affinity. However, whereas 3 0 -truncated cDNA expression versions of various cytokine genes have already been used in many studies, [22][23][24][25] their utility as compared to 3 0 UTR-containing or AUGUAmutated constructs has not undergone systematic study. In this study, we investigated modifications of cytokine cDNA expression vectors, in which either the AUUUA pentamer reiterations were replaced with a mutant form (AUGUA) Â 4 or the 3 0 UTR was completely deleted/removed to inhibit the binding of mRNA degrading proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Transfected tissues were homogenized, centrifuged and the supernatant was quantitatively assayed for specific cytokines using corresponding ELISA kit assays as previously described. 3,5,23,29 For others, see footnote in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Molecular strategies for improving cytokine transgene expression in normal and malignant tissues

Turner

2003

Gene Ther

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The augmentation and optimization of specific targeted transgene expression systems are important strategies for clinical research into gene therapy and DNA vaccination, due to safety considerations. In this study, we introduced 3 0 untranslated regions and transcriptional control modifications and direct tandem or combinational vector design strategies into a number of specific cytokine cDNA expression plasmids. The experiments were performed in parallel using both in vivo and in vitro transgene expression systems. In vivo studies were carried out using gene gun delivery of test vectors into mouse skin tissues. A combination of specific cell lines and fresh cell explants were used for in vitro and ex vivo transgene expression assay systems. The results from these comparative experiments demonstrated that a number of molecular biology manipulations can be readily adapted to define and significantly enhance the level or/and duration of transgene expression for a group of clinically relevant cytokine genes, with very similar effects for both in vivo and in vitro test systems. This cytokine transgene expression system may offer a favorable means for improving the efficiency of cytokine gene therapy and DNA vaccines in future clinical studies.

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“…For instance, the turnover rate of GM-CSF message in cord blood mononuclear cells is three times faster than in adult mononuclear cells because of increased AUF1 levels and activity. 106,107 AUF1 may also choreograph different turnover rates of gene variants. A short-lived polymorphic variant of thymidylate synthase was shown preferentially to bind AUF1, leading to its decay.…”

Section: Destabilizing Proteinsmentioning

confidence: 99%

mRNA stability control: a clandestine force in normal and malignant hematopoiesis

Steinman

2007

Leukemia

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This review addresses the scope of influence of mRNA decay on cellular functions and its potential role in normal and malignant hematopoiesis. Evidence is emerging that leukemic oncogenes and hematopoietic cytokines interact with mRNA decay pathways. These pathways can co-regulate functionally related genes through specific motifs in the 3 0 -untranslated region of targeted transcripts. The steps that link external stimuli to transcript turnover are not fully understood, but include subcellular relocalization or post-transcriptional modification of specific transcript-stabilizing or -destabilizing proteins. Improper functioning of these regulators of mRNA turnover can impede normal cellular differentiation or promote cancers. By delineating how subsets of transcripts decay in synchrony during normal hematopoiesis, it may be possible to determine whether this post-transcriptional regulatory pathway is hijacked in leukemogenesis.

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Developmental Regulation of RNA Transcript Destabilization by A + U-rich Elements is AUF1-dependent

Cited by 59 publications

References 65 publications

Tristetraprolin Binds to the 3′-Untranslated Region of Cyclooxygenase-2 mRNA

Tristetraprolin Binds to the 3′-Untranslated Region of Cyclooxygenase-2 mRNA

Molecular strategies for improving cytokine transgene expression in normal and malignant tissues

mRNA stability control: a clandestine force in normal and malignant hematopoiesis

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