Translational control by the 3′-UTR: the ends specify the means

Mazumder, Barsanjit; Seshadri, Vasudevan; Fox, Paul L.

doi:10.1016/s0968-0004(03)00002-1

Cited by 451 publications

(348 citation statements)

References 53 publications

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“…(1,8,17,19,20,31,32). The 3′UTRs of mRNAs are preferred target sites for miRs and play an essential role in translational control and in the stability of transcripts (13,33). MiR-125b has been recently described to target erbB2 mRNA (30).…”

Section: Introductionmentioning

confidence: 99%

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Hofmann

Heinrich

Radziwil

et al. 2009

Molecular Cancer Research

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The noncoding RNA miR-125b has been described to reduce ErbB2 protein expression as well as proliferation and migration of cancer cell lines. As additional target of miR-125b, we identified the c-raf-1 mRNA by sequence analysis. We designed a short hairpin-looped oligodeoxynucleotide (ODN) targeted to the same 3′ untranslated region of c-raf-1 mRNA as miR-125b. The fully complementary ODN antisense strand is linked to a second strand constituting a partially double-stranded structure of the ODN. Transfection of the c-raf-1-specific ODN (ODN-Raf) in a breast cancer cell line reduced the protein levels of C-Raf, ErbB2, and their downstream effector cyclin D1 similar to miR-125b. MiR-125b as well as ODN-Raf showed no effect on the c-raf-1 mRNA level in contrast to small interfering RNA. Unlike miR-125b, ODN-Raf induced a cytopathic effect. This may be explained by the structural properties of ODN-Raf, which can form G-tetrads. Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death. Both features may be useful to interfere with tumor growth. (Mol Cancer Res 2009;7(10):1635-44)

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Section: Introductionmentioning

confidence: 99%

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Hofmann

Heinrich

Radziwil

et al. 2009

Molecular Cancer Research

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“…The length of 3Ј-UTRs increases with evolutionary age and organism complexity (with human mRNAs having the longest 3Ј-UTRs (Pesole et al 2002;Mazumder et al 2003). The longer 3Ј-UTRs may provide more regulatory elements that may contribute to a more complex posttranscriptional regulation of mRNAs in humans.…”

Section: Human Microrna Targets Genes and Development 1173mentioning

confidence: 99%

A combined computational-experimental approach predicts human microRNA targets

Kiriakidou¹,

Nelson²,

Kouranov³

et al. 2004

Genes Dev.

709

502

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A new paradigm of gene expression regulation has emerged recently with the discovery of microRNAs (miRNAs). Most, if not all, miRNAs are thought to control gene expression, mostly by base pairing with miRNA-recognition elements (MREs) found in their messenger RNA (mRNA) targets. Although a large number of human miRNAs have been reported, many of their mRNA targets remain unknown. Here we used a combined bioinformatics and experimental approach to identify important rules governing miRNA-MRE recognition that allow prediction of human miRNA targets. We describe a computational program, "DIANA-microT", that identifies mRNA targets for animal miRNAs and predicts mRNA targets, bearing single MREs, for human and mouse miRNAs. bros 1999;Seggerson et al. 2002;Zeng et al. 2002;Doench et al. 2003). The manner by which a miRNA or siRNA base pairs with its mRNA target correlates with its function: if the complementarity between a miRNA and its target is extensive, the RNA target is cleaved (Hutvagner and Zamore 2002;Llave et al. 2002;Rhoades et al. 2002;Tang et al. 2003;Xie et al. 2003); if the complementarity is partial, the stability of the target mRNA in not affected but its translation is repressed (Olsen and Ambros 1999;Seggerson et al. 2002;Zeng et al. 2002;Doench et al. 2003). However, how general this correlation is and the factors and mechanisms that determine the function of any given miRNA are unknown.

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“…32,33). We examined the expression of luciferase in cells transfected with plasmids containing the complete 5Ј-UTR of TSP-1 cloned in front of the luciferase cDNA, the complete 3Ј-UTR cloned immediately at the 3Ј of the luciferase cDNA, or both 5Ј and 3Ј-UTR.…”

Section: Increased Tsp-1 Production In Macrovascular Ec-wementioning

confidence: 99%

Cell Type-specific Post-transcriptional Regulation of Production of the Potent Antiangiogenic and Proatherogenic Protein Thrombospondin-1 by High Glucose

Bhattacharyya

Marinic

Krukovets

et al. 2008

Journal of Biological Chemistry

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Hyperglycemia is an independent risk factor for development of vascular diabetic complications. Vascular dysfunction in diabetics manifests in a tissue-specific manner; macrovasculature is affected by atherosclerotic lesions, and microvascular complications are described as "aberrant angiogenesis": in the same patient angiogenesis is increased in some tissues (e.g. retinal neovascularization) and decreased in others (e.g. in skin). Molecular cell-and tissue-specific mechanisms regulating the response of vasculature to hyperglycemia remain unclear. Thrombospondin-1 (TSP-1), a potent antiangiogenic and proatherogenic protein, has been implicated in the development of several vascular diabetic complications (atherosclerosis, nephropathy, and cardiomyopathy). This study examines cell type-specific regulation of production of thrombospondin-1 by high glucose. We previously reported the increased expression of TSP-1 in the large arteries of diabetic animals. mRNA and protein levels were up-regulated in response to high glucose. Unlike in macrovascular cells, TSP-1 protein levels are dramatically decreased in response to high glucose in microvascular endothelial cells and retinal pigment epithelial cells (RPE). This downregulation is post-transcriptional; mRNA levels are increased. In situ mRNA hybridization and immunohistochemistry revealed that the level of mRNA is up-regulated in RPE of diabetic rats, whereas the protein level is decreased. This cell type-specific posttranscriptional suppression of TSP-1 production in response to high glucose in microvascular endothelial cells and RPE is controlled by untranslated regions of TSP-1 mRNA that regulate coupling of TSP-1 mRNA to polysomes and its translation. The cellspecific regulation of TSP-1 suggests a potential mechanism for the aberrant angiogenesis in diabetics and TSP-1 involvement in development of various vascular diabetic complications.Despite the significant advances in the therapeutic methods to control blood glucose and insulin levels in diabetic patients, the precise regulation of these levels remains a problem. Vascular diabetic complications remain most prevalent and dangerous and account for the greatest numbers of deaths and hospitalizations in diabetic patients. The molecular basis for the vascular complications of diabetes is not well understood. Recent reports indicate that both microvascular and macrovascular complications of diabetes correlate directly with glucose levels in both patients and animal models (1-5). Some of these reports revealed the pathogenic role of impaired glucose tolerance and post-prandial hyperglycemia even in the absence of diabetes, e.g. (6). In vascular cells, glucose regulates expression of many genes that have been linked to the development of atherosclerosis or abnormal angiogenesis (reviewed in Ref. 7). One of them is thrombospondin-1 (TSP-1), 3 a cell matrix protein implicated in both atherogenesis (8 -12) and angiogenesis (13)(14)(15)(16)(17)(18)(19). Several lines of evidence indicate that TSP-1 may represent a lin...

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Translational control by the 3′-UTR: the ends specify the means

Cited by 451 publications

References 53 publications

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

A combined computational-experimental approach predicts human microRNA targets

Cell Type-specific Post-transcriptional Regulation of Production of the Potent Antiangiogenic and Proatherogenic Protein Thrombospondin-1 by High Glucose

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