Messenger RNA degradation in eukaryotes

Sachs, Alan B.

doi:10.1016/0092-8674(93)80043-e

Cited by 822 publications

(465 citation statements)

References 61 publications

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“…The 3Ј UTR of the IL-1␣ transcript is AU rich (ARE), and contains at least six copies of the Shaw-Kamens sequence (ATTTA) (28,45). This motif is present in many immediate early genes and is thought to be involved in regulating the rate of mRNA degradation (46). The IL-1␣ mRNA was relatively unstable with a half-life of 2 h. There was a significant reduction in the IL-1␣ mRNA decay rate in PGE 2 -stimulated LS-174T cells as compared with vehicle-treated cells.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Induces the Expression of IL-1α in Colon Cancer Cells

Shao

Sheng

2007

The Journal of Immunology

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PGE2 has been shown to exert pro-oncogenic effects in colorectal neoplasia through producing autocrine or paracrine growth factors. In the present study, we demonstrate that PGE2 induced the expression of IL-1α in colon cancer cells, which plays critical roles in tumor metastasis and neoangiogenesis in a variety of cancers. PGE2 increased the levels of both IL-1α mRNA and protein, suggesting a positive feedback loop between the IL-1 pathway and PGE2 signaling. Mechanistically, PGE2 induced the expression of IL-1α at both transcriptional and posttranscriptional levels. PGE2 stimulated the transcriptional activity of the IL-1α promoter and significantly stabilized IL-1α mRNA. Moreover, we show that IL-1α enhanced colorectal neoplasia, stimulating cell migration and neoangiogenesis. Knockdown of the expression of IL-1α by small-interfering RNA resulted in a reduction of vascular endothelial growth factor secretion in colon cancer cells and an inhibition of tube formation by HUVECs. Thus, our results suggest that PGE2 induces the expression of proinflammatory cytokine IL-1α, which may potentially enhance the proneoplastic actions of the cyclooxygenase-2/PGE2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Induces the Expression of IL-1α in Colon Cancer Cells

Shao

Sheng

2007

The Journal of Immunology

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“…The steady-state levels of highly regulated mRNAs are markedly influenced by the rate of degradation [1,36,37], and there is evidence that G-protein-coupled receptors, such as the AT "A receptor, are regulated by agonist-induced mRNA destabilization. This has been shown previously for two G-protein coupled receptors, the M1 muscarinic acetylcholine receptor [38] and the β-adrenergic receptor [39].…”

Section: Discussionmentioning

confidence: 99%

Functional role for the angiotensin II receptor (AT1A) 3′-untranslated region in determining cellular responses to agonist: evidence for recognition by RNA binding proteins

Thekkumkara

Gruber

Motel

et al. 1998

Biochemical Journal

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We demonstrate a functional role for the 3ʹ-untranslated region (3ʹ-UTR) of the angiotensin II (Ang II) receptor subtype AT1A mRNA in Chinese hamster ovary (CHO-K1) cells by stably transfecting the coding region of the receptor gene with or without the 845 bp 3ʹ-UTR. Two cell lines expressing similar levels of cell-surface receptors (with 3ʹ-UTR, Bmax = 571 fmol/mg protein; without 3ʹ-UTR, Bmax = 663 fmol/mg protein) were used in the present study. Both cell lines expressed high-affinity receptors (with 3ʹ-UTR, Kd = 0.83 nM; without 3ʹ-UTR, Kd = 0.82 nM), and binding studies with 125I-labelled Ang II in the presence of GTP[S] demonstrated that both coupled to heterotrimeric G-proteins. Despite these similarities, significant differences were observed for receptor-mediated cell signalling pathways. In cells without the 3ʹ-UTR, Ang II stimulated an increase in cAMP accumulation (11-fold above control) and in cells with the 3ʹ-UTR no stimulation was observed, which was consistent with previous observations in most endogenous Ang II receptor (AT1)-expressing cells. Activation of cAMP by Ang II in cells without the 3ʹ-UTR correlated with an inhibition of DNA synthesis, determined by [3H]thymidine incorporation. Ang II-mediated responses were blocked by EXP3174, a selective non-peptide receptor antagonist. We also observed differences in the transient profiles of intracellular calcium between cells with and without the 3ʹ-UTR in response to Ang II. In cells with the 3ʹ-UTR, a sustained level of intracellular calcium was observed after Ang II stimulation, whereas cells without the 3ʹ-UTR displayed a full return to basal level within 50 s of Ang II treatment. Even though the expressed exogenous gene is under the control of a constitutively expressing promoter (cytomegalovirus promoter), Northern-blot analysis revealed a considerably greater accumulation of AT1A mRNA in cells without the 3ʹ-UTR compared with cells with the 3ʹ-UTR. Analysis of the decay rate of the AT1A mRNA in cells with and without the 3ʹ-UTR revealed that the normally unstable AT1A receptor mRNA became highly stable by removing its 3ʹ-UTR, identifying a role for the 3ʹ-UTR in mRNA destabilization. Interestingly, both cells express similar levels of receptors at the cell surface, suggesting that the 3ʹ-UTR is also involved in the efficient translation and/or translocation of the receptor protein to the plasma membrane. We hypothesized that these 3ʹ-UTR-mediated functions of the receptor are regulated by RNA-binding proteins. To identify possible RNA-binding proteins for the AT1A 3ʹ-UTR, cellular extracts were prepared from parental CHO-K1 cells and 3ʹ-UTR-binding assays, electrophoretic mobility-shift assays and UV crosslinking studies were performed. A major cellular protein of 55 kDa was identified, which specifically interacted with the 3ʹ-UTR. Our data suggest that the 3ʹ-UTR of the AT1A can control specific receptor functions, perhaps via selective recognition of the 3ʹ-UTR by RNA-binding proteins.

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“…HuD and Hel-N1 bind in vitro to AU-rich elements in the 3'-untranslated regions (3'-UTR) of mRNAs Gao et al, 1994;Jain et al, 1997;King et al, 1994;Levine et al, 1993;Liu et al, 1995). Other proteins binding AUrich sequences have been shown to destabilize mRNAs encoding growth-regulatory proteins (Brawerman, 1989;Sachs, 1993;Shaw and Kamen, 1986), participate in the regulation of RNA splicing (McCullough and Schuler, 1993;Singh et al, 1995), and transport messages from the nucleus (Muller et al, 1992). This suggests that one or several of the Hu proteins might participate in nuclear processing or transport of N-myc RNA.…”

Section: Introductionmentioning

confidence: 99%

HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing/stability in malignant human neuroblasts

et al. 1999

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N-myc gene copy numbers and transcription rates are similar in N (neuroblastic, tumorigenic) and S (nonneuronal, non-tumorigenic) neuroblastoma cells with chromosomally integrated ampli®ed N-myc genes. However, N cells show signi®cantly higher N-myc mRNA levels than S cells. Therefore, post-transcriptional control of N-myc gene expression must di er between these cell types. Since no di erences in N-myc mRNA half-life were found between N and S cells from two cell lines, steady-state levels of N-myc pre-mRNA processing intermediates were analysed. Results suggest that the di erences in N-myc expression arise primarily at the nuclear post-transcriptional level. The neuronal-speci®c RNA-binding Hu proteins are present in cytoplasmic and nuclear fractions of N cells and one of them, HuD, binds speci®cally to both exonic and intronic N-myc RNA sequences. In sense and antisense HuD-transfected N cells, there are coordinate changes in HuD and N-myc expression levels. Thus, we propose that HuD plays a role in the nuclear processing/stability of N-myc premRNA in N-type neuroblastoma cells.

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Messenger RNA degradation in eukaryotes

Cited by 822 publications

References 61 publications

Prostaglandin E2 Induces the Expression of IL-1α in Colon Cancer Cells

Prostaglandin E2 Induces the Expression of IL-1α in Colon Cancer Cells

Functional role for the angiotensin II receptor (AT1A) 3′-untranslated region in determining cellular responses to agonist: evidence for recognition by RNA binding proteins

HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing/stability in malignant human neuroblasts

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