mRNA Silencing in Erythroid Differentiation: hnRNP K and hnRNP E1 Regulate 15-Lipoxygenase Translation from the 3′ End

Ostareck, Dirk H.; Ostareck-Lederer, Antje; Wilm, Matthias; Thiele, B; Mann, Matthias; Hentze, Matthias W.

doi:10.1016/s0092-8674(00)80241-x

Cited by 464 publications

(452 citation statements)

References 48 publications

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“…These properties suggest that K protein bridges signal transduction pathways to nucleic aciddirected processes. In further support of this model, several studies have shown that K protein can alter rates of transcription (Michelotti et al, 1996) and translation (Ostareck et al, 1997).…”

mentioning

confidence: 75%

Nuclear shift of hnRNP K protein in neoplasms and other states of enhanced cell proliferation

Ostrowski

Bomsztyk

2003

Br J Cancer

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The heterogeneous nuclear ribonucleoprotein K (hnRNP K), is a ubiquitously expressed protein that interacts with signal transducers, proteins that modulate gene expression and selective RNA and DNA motifs. K protein is modified in response to extracellular signals and directly regulates rates of transcription and translation. We used serum-treated hepatocyte culture, liver after partial hepatectomy and hepatic neoplasms as systems to compare expression, subcellular distribution and tyrosine phosphorylation of K protein in quiescent and dividing cells. The results show that expression of K protein mRNA was increased in states of enhanced proliferation. Levels of nuclear K protein were also higher in proliferating compared to resting cells. In contrast, levels of cytoplasmic K protein were the same or lower in dividing compared to quiescent cells. States of enhanced proliferation were also associated with increased levels of K protein tyrosine phosphorylation. Nuclear shift of K protein in dividing cells may reflect involvement of K protein in signalling multiple events that regulate expression of genes in proliferating cells.

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mentioning

confidence: 75%

Nuclear shift of hnRNP K protein in neoplasms and other states of enhanced cell proliferation

Ostrowski

Bomsztyk

2003

Br J Cancer

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“…Recent work has revealed an unexpected role of several members of the SR protein family, including ASF/SF2 and SRp20, in translational control (Sanford et al, 2004;Bedard et al, 2007). Among the hnRNP family, hnRNP K and hnRNP E1 silence translation of the 15-lipoxygenase (LOX) mRNA in immature erythroid precursor cells (Ostareck et al, 1997). Several hnRNPs, including A1, C1/C2, E1/E2, I (PTB), and L, are independently involved in the translational control of specific mRNAs containing internal ribosome entry sites (IRESs) through a capindependent mechanism (for review, see Vagner et al, 2001;Bonnal et al, 2003;Komar and Hatzoglou, 2005).…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic Relocalization of Heterogeneous Nuclear Ribonucleoprotein A1 Controls Translation Initiation of Specific mRNAs

Cammas

Pileur

Bonnal

et al. 2007

MBoC

136

130

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Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a nucleocytoplasmic shuttling protein that regulates gene expression through its action on mRNA metabolism and translation. The cytoplasmic redistribution of hnRNP A1 is a regulated process during viral infection and cellular stress. Here, we show that hnRNP A1 is an internal ribosome entry site (IRES) trans-acting factor that binds specifically to the 5 untranslated region of both the human rhinovirus-2 and the human apoptotic peptidase activating factor 1 (apaf-1) mRNAs, thereby regulating their translation. Furthermore, the cytoplasmic redistribution of hnRNP A1 after rhinovirus infection leads to enhanced rhinovirus IRES-mediated translation, whereas the cytoplasmic relocalization of hnRNP A1 after UVC irradiation limits the UVC-triggered translational activation of the apaf-1 IRES. Therefore, this study provides a direct demonstration that IRESs behave as translational enhancer elements regulated by specific trans-acting mRNA binding proteins in given physiological conditions. Our data highlight a new way to regulate protein synthesis in eukaryotes through the subcellular relocalization of a nuclear mRNA-binding protein.

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“…There is a short, but growing, list of genes containing RNA cis-elements that modulate translation: the transcript for FMR protein (Fragile X mental retardation protein) encodes 5 0 UTR secondary structure, which is sufficiently stable to suppress downstream FMR protein translation (Feng et al, 1995), tissue-specific regulation of fibroblast growth factor 2 translation appears to be dependent on its 5 0 UTR (Creancier et al, 2000), 15-lipoxygenase, fibronectin, lipoprotein lipase, folate receptor-a, interferon-g, transforming growth factor-b1, m-numb and neural nitric-oxide synthase (nNOS), among others (Ostareck et al, 1997;Ranganathan et al, 2000;Galy et al, 2001;Morrisey et al, 2001;Imai et al, 2001;Ben-Asouli et al, 2002). Similarly, vascular endothelial growth factor regulation by hypoxia (Stein et al, 1998) and platelet-derived growth factor 2/c-sis expression that occurs during differentiation (Bernstein et al, 1997) are regulated in this way as well.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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Adrenomedullin (AM) is a multifunctional regulatory peptide with important angiogenic and mitogenic properties. Here we identify a region of stable secondary structure in the 5 0 -untranslated region (5 0 UTR) of human AM mRNA. Reverse transcriptase-polymerase chain reaction of the 5 0 UTR consistently resulted, in addition to the product with the expected size of 155 base pair (bp), in a second product with an B65-bp deletion from the central region of the 5 0 UTR, suggesting the presence of a secondary structure. The presence of a stem-loop structure was confirmed by probing the 5 0 UTR with RNases with selectivity for single-or double-stranded RNA. We investigated the role of this stem-loop structure in expression of luciferase reporter gene in cultured cell lines. Reporter assays using a chimeric mRNA that combined luciferase and the 5 0 UTR of AM mRNA demonstrated a dramatic decrease of the reporter activity owing to a decreased translation, whereas the deletion of the stem-loop structure localized between nt þ 31 and þ 95 from the cap site led to the recovery of activity. Gel migration shift assays using cytosolic extracts from mammalian cell lines demonstrate a specific binding of a cytosolic protein to riboprobes containing the 5 0 UTR of AM but not to riboprobes either corresponding to other areas of the message or containing the 5 0 UTR but lacking the region of secondary structure. Although we conclude that the 5 0 UTR of the human AM mRNA can modulate the translation of AM mRNA in vivo, and that the predicted stem-loop structure is necessary for this inhibition, the functional consequences of the cis element-binding activity remain to be determined.

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mRNA Silencing in Erythroid Differentiation: hnRNP K and hnRNP E1 Regulate 15-Lipoxygenase Translation from the 3′ End

Cited by 464 publications

References 48 publications

Nuclear shift of hnRNP K protein in neoplasms and other states of enhanced cell proliferation

Nuclear shift of hnRNP K protein in neoplasms and other states of enhanced cell proliferation

Cytoplasmic Relocalization of Heterogeneous Nuclear Ribonucleoprotein A1 Controls Translation Initiation of Specific mRNAs

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

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