Regulation of the murine inducible nitric oxide synthase gene by dexamethasone involves a heterogeneous nuclear ribonucleoprotein I (hnRNPI) dependent pathway

Söderberg, Malin; Raffalli-Mathieu, Françoise; Lang, Matti A.

doi:10.1016/j.molimm.2007.01.029

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…Only when the CU‐rich core is deleted does a second, stronger complex bind, which we would predict based on our super‐shift assays is composed of hnRNPL alone. This interaction is similar to what has been previously reported showing that hnRNPL and PTB heterodimerize 52,53 and bind to the murine inducible nitric oxide synthase 3′ UTR upon glucocorticoid activation 54 …”

Section: Discussionsupporting

confidence: 91%

“…This interaction is similar to what has been previously reported showing that hnRNPL and PTB heterodimerize 52,53 and bind to the murine inducible nitric oxide synthase 3 0 UTR upon glucocorticoid activation. 54 In conclusion, we have shown that the CD40L A+B+C region functions on its own in vivo as a stability element to redirect the turnover of a heterologous transcript. We have also independently analysed both the first and third stability regions and characterized proteins that bind to specific sites.…”

Section: Discussionmentioning

confidence: 68%

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Functional analysis of a tripartite stability element within the CD40 ligand 3′ untranslated region

et al. 2008

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SummaryWe previously identified a cis-acting element within the 3 0 untranslated region of CD40 ligand messenger RNA (mRNA) that is composed of three complex binding sites and acts to increase mRNA stability in both in vitro and in vivo systems. We now demonstrate the functional consequences of the three binding sites with respect to increasing both luciferase activity and mRNA stability in a heterologous transcript expressed in a T-cell line. The internal region B was shown to be a bona fide stability element because its presence increased luciferase activity fourfold over the unmodified transcript and its removal from the XbaI-HaeIII region resulted in rapid degradation of the transcript. Region A contained both a binding site for a polypyrimidine-tract-binding protein (PTB)-mediated complex (Complex I) and an upstream, adjacent sequence that was a negative regulator of mRNA stability. Region C bound Complex II, which contained both PTB and heterogeneous nuclear ribonucleoproteinL (hnRNPL), and was less effective as a stability element on its own compared to region B. Our findings demonstrate differential levels of activity for the three binding sites relative to the turnover of CD40 ligand mRNA, suggesting that the lack of binding of Complex I/II during the early stages of T-cell activation contributes to the rapid degradation of the CD40 ligand mRNA transcript.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 68%

Functional analysis of a tripartite stability element within the CD40 ligand 3′ untranslated region

et al. 2008

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“…It has been shown to repress the inclusion of alternative exons in numerous systems. Recently, hnRNP I was shown to bind to the 3′UTR of inducible nitric oxide synthase mRNA, and the binding was correlated with mRNA destabilization (43). In this study, we show that hnRNP I is a decay-promoting factor for the LDLR transcript through its binding to ARE motifs.…”

Section: Identification Of Ldlr Mrna Binding Proteins 827mentioning

confidence: 51%

Identification of mRNA binding proteins that regulate the stability of LDL receptor mRNA through AU-rich elements

Chen

Zhou

et al. 2009

Journal of Lipid Research

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The 3′untranslated region (UTR) of human LDL receptor (LDLR) mRNA contains three AU-rich elements (AREs) responsible for rapid mRNA turnover and mediates the stabilization induced by berberine (BBR). However, the identities of the specific RNA binding proteins involved in the regulation of LDLR mRNA stability at the steady state level or upon BBR treatment are unknown. By conducting small interfering RNA library screenings, biotinylated RNA pull-down, mass spectrometry analysis, and functional assays, we now identify heterogeneous nuclear ribonucleoprotein D (hnRNP D), hnRNP I, and KH-type splicing regulatory protein (KSRP) as key modulators of LDLR mRNA stability in liver cells. We show that hnRNP D, I, and KSRP interact with AREs of the LDLR 3′UTR with sequence specificity. Silencing the expression of these proteins increased LDLR mRNA and protein levels. We further demonstrate that BBR-induced mRNA stabilization involves hnRNP I and KSRP, as their cellular depletions abolished the BBR effect and BBR treatment reduced the binding of hnRNP I and KSRP to the LDLR mRNA 3′UTR. These new findings demonstrate that LDLR mRNA stability is controlled by a group of ARE binding proteins, including hnRNP D, hnRNP I, and KSRP. Our results suggest that interference with the ability of destabilizing ARE binding proteins to interact with LDLR-ARE motifs is likely a mechanism for regulating LDLR expression by compounds such as BBR and perhaps

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“…In the macrophage, hnRNPs regulate iNOS expression by binding to the 3′-untranslated region of iNOS mRNA tagging it for degradation. With cytokine stimulation, hnRNP levels and hnRNP-iNOS mRNA complex formation decrease resulting in greater iNOS protein expression [112,113]. iNOS activity, in turn, has been shown to induce S-nitrosylation of hnRNP A/B inhibiting its binding to the osteopontin promoter in cytokine-stimulated macrophages [114,115].…”

Section: S-nitrosylation Of Mammalian Transcription Factorsmentioning

confidence: 99%

S-nitrosylation in the regulation of gene transcription

Sha

Marshall

2012

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Post-translational modification of proteins by S-nitrosylation serves as a major mode of signaling in mammalian cells and a growing body of evidence has shown that transcription factors and their activating pathways are primary targets. S-nitrosylation directly modifies a number of transcription factors, including NF-κB, HIF-1, and AP-1. In addition, S-nitrosylation can indirectly regulate gene transcription by modulating other cell signaling pathways, in particular JNK kinase and ras. Scope of review The evolution of S-nitrosylation as a signaling mechanism in the regulation of gene transcription, physiological advantages of protein S-nitrosylation in the control of gene transcription, and discussion of the many transcriptional proteins modulated by S-nitrosylation is summarized. Major conclusions S-nitrosylation plays a crucial role in the control of mammalian gene transcription with numerous transcription factors regulated by this modification. Many of these proteins serve as immunomodulators, and inducible nitric oxide synthase (iNOS) is regarded as a principal mediatiator of NO-dependent S-nitrosylation. However, additional targets within the nucleus (e.g. histone deacetylases) and alternative mechanisms of S-nitrosylation (e.g. GAPDH-mediated trans-nitrosylation) are thought to play a role in NOS-dependent transcriptional regulation. General significance Derangement of SNO-regulated gene transcription is an important factor in a variety of pathological conditions including neoplasia and sepsis. A better understanding of protein S-nitrosylation as it relates to gene transcription and the physiological mechanisms behind this process is likely to lead to novel therapies for these disorders. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.

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Regulation of the murine inducible nitric oxide synthase gene by dexamethasone involves a heterogeneous nuclear ribonucleoprotein I (hnRNPI) dependent pathway

Cited by 13 publications

References 31 publications

Functional analysis of a tripartite stability element within the CD40 ligand 3′ untranslated region

Functional analysis of a tripartite stability element within the CD40 ligand 3′ untranslated region

Identification of mRNA binding proteins that regulate the stability of LDL receptor mRNA through AU-rich elements

S-nitrosylation in the regulation of gene transcription

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