Identification of secondary structure in the 5′-untranslated region of the human adrenomedullin mRNA with implications for the regulation of mRNA translation

Brenet, Fabienne; Dussault, Nadège; Delfino, Christine; Boudouresque, Françoise; Chinot, Olivier; Pm, Martin; Ouafik, L’Houcine

doi:10.1038/sj.onc.1209672

Cited by 9 publications

(5 citation statements)

References 52 publications

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“…Stable secondary RNA structures in the 5′-UTRs of mRNAs have been shown to regulate translation ,− . In fact, RNA G-quadruplexes containing short or one-nucleotide loops have been found to be extremely stable and can inhibit translation ,, .…”

Section: Discussionmentioning

confidence: 99%

An Unusually Stable G-Quadruplex within the 5′-UTR of the MT3 Matrix Metalloproteinase mRNA Represses Translation in Eukaryotic Cells

2009

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MT3-MMP is a matrix metalloproteinase involved in the regulation of cancer cell invasion and metastasis. The MT3-MMP mRNA contains a 20-nucleotide G-rich region (M3Q) upstream of the initiation codon. Herein, we report that the M3Q purine-only sequence forms an extremely stable intramolecular G-quadruplex structure and has an inhibitory role on translation of a reporter gene in eukaryotic cells. The formation of the G-quadruplex structure was indicated by circular dichroism (CD) spectroscopy and enzymatic footprinting with RNase T1. The unusual stability of the G-quadruplex was evidenced when addition of only 1 mM KCl resulted in about a 30 degrees C increase in the melting temperature (T(m)), as compared to that obtained in the absence of added salt. The T(m) was independent of the RNA concentration, suggesting an intramolecular G-quadruplex structure. Additionally, in a dual luciferase reporter assay performed in eukaryotic cells, the M3Q motif present in the context of the entire 5'-UTR of MT3-MMP repressed activity of its downstream gene by more than half. To the best of our knowledge, the naturally occurring M3Q sequence forms one of the most stable, intramolecular RNA G-quadruplexes reported. This report is the first to establish a functional role of a G-quadruplex forming sequence within the MT3-MMP 5'-UTR in the regulation of translation in eukaryotic cells.

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Section: Discussionmentioning

confidence: 99%

An Unusually Stable G-Quadruplex within the 5′-UTR of the MT3 Matrix Metalloproteinase mRNA Represses Translation in Eukaryotic Cells

2009

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“…26,[28][29][30][31][32][33] A stem-loop structure in exon 1 of the human ADM gene has been reported that participates in the regulation of ADM transcription. 34 In mice, the ADM gene is located in chromosome 7. It has an amino acid similarity of 60% with the human ADM gene.…”

Section: Gene Structurementioning

confidence: 99%

Regulation of endothelial and epithelial barrier functions by peptide hormones of the adrenomedullin family

et al. 2016

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The correct regulation of tissue barriers is of utmost importance for health. Barrier dysfunction accompanies inflammatory disorders and, if not controlled properly, can contribute to the development of chronic diseases. Tissue barriers are formed by monolayers of epithelial cells that separate organs from their environment, and endothelial cells that cover the vasculature, thus separating the blood stream from underlying tissues. Cells within the monolayers are connected by intercellular junctions that are linked by adaptor molecules to the cytoskeleton, and the regulation of these interactions is critical for the maintenance of tissue barriers. Many endogenous and exogenous molecules are known to regulate barrier functions in both ways. Proinflammatory cytokines weaken the barrier, whereas anti-inflammatory mediators stabilize barriers. Adrenomedullin (ADM) and intermedin (IMD) are endogenous peptide hormones of the same family that are produced and secreted by many cell types during physiologic and pathologic conditions. They activate certain G-protein-coupled receptor complexes to regulate many cellular processes such as cytokine production, actin dynamics and junction stability. In this review, we summarize current knowledge about the barrier-stabilizing effects of ADM and IMD in health and disease.

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“…Commonly, the secondary structures of the 5Ј UTR have been characterized as down-regulators of gene expression. They are capable of inhibiting gene transcription process (Curie and McCormick 1997), accelerating mRNA degradation rate (Muhlrad et al 1995;Stefanovic et al 2000;Cannons and Cannon 2002), or reducing translation eYciency (Kozak 1989;Vega Laso et al 1993;Muhlrad et al 1995;Hess and Duncan 1996;Wood et al 1996;McCarthy 1998;Hua et al 2001;Myers et al 2004;Brenet et al 2006;Bunimov et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of 5′ untranslated region of a TIR-NBS-encoding gene from triploid white poplar

et al. 2009

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Genome-wide analyses have identified a set of TIR-NBS-encoding genes in plants. However, the molecular mechanism underlying the expression of these genes is still unknown. In this study, we presented a TIR-NBS-encoding gene, PtDrl02, that displayed a low level of tissue-specific expression in a triploid white poplar [(Populus tomentosa x P. bolleana) x P. tomentosa], and analyzed the effects of the 5' untranslated region (UTR) on gene expression. The 5' UTR sequence repressed the reporter activity of beta-glucuronidase (GUS) gene under PtDrl02 promoter by 113.5-fold with a staining ratio of 2.97% in the transgenic tobacco plants. Quantitative RT-PCR assays revealed that the 5' UTR sequence decreased the transcript level of the GUS reporter gene by 13.3-fold, implying a regulatory role of 5' UTR in transcription and/or mRNA destabilization. The comparison of GUS activity with the transcript abundance indicated that the 5' UTR sequence decreased the translation efficiency of target gene by 88.3%. Additionally, the analysis of the transgenic P-985/UTRDelta/GUS plants showed that both the exon1 sequence and the leading intron within the 5' UTR region were responsible for the regulation of gene expression. Our results suggested a negative effect of the 5' UTR of PtDrl02 gene on gene expression.

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Identification of secondary structure in the 5′-untranslated region of the human adrenomedullin mRNA with implications for the regulation of mRNA translation

Cited by 9 publications

References 52 publications

An Unusually Stable G-Quadruplex within the 5′-UTR of the MT3 Matrix Metalloproteinase mRNA Represses Translation in Eukaryotic Cells

An Unusually Stable G-Quadruplex within the 5′-UTR of the MT3 Matrix Metalloproteinase mRNA Represses Translation in Eukaryotic Cells

Regulation of endothelial and epithelial barrier functions by peptide hormones of the adrenomedullin family

Functional analysis of 5′ untranslated region of a TIR-NBS-encoding gene from triploid white poplar

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