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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The translational activation of dormant tissue-type plasminogen activator mRNA during meiotic maturation of mouse oocytes is accompanied by elongation of its 3'-poly(A) tract. Injected RNA fragments that correspond to part of the 3'-untranslated region (3'UTR) of this mRNA are also subject to regulated polyadenylation. Chimeric mRNAs containing part of this 3'UTR are polyadenylated and translated following resumption of meiosis. Polyadenylation and translation of chimeric mRNAs require both specific sequences in the 3'UTR and the canonical 3'-processing signal AAUAAA. Injection of 3'-blocked mRNAs and in vitro polyadenylated mRNAs shows that the presence of a long poly(A) tract is necessary and sufficient for translation. These results establish a role for regulated polyadenylation in the post-transcriptional control of gene expression.
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PMID:Regulated polyadenylation controls mRNA translation during meiotic maturation of mouse oocytes. 248 95

A series of t-PA cDNA mutants containing different parts of 3'-UTR sequences have been constructed. In vitro translation of t-PA transcripts in rabbit reticulocyte lysates and its expression in COS-7 cells show that the 3'-UTR sequence has a very strong inhibitory effect on t-PA translation. The deletion of 3'-UTR results in 3-8-fold increase of t-PA expression. Further study shows that an AU-rich sequence of some 200 nt at 3' end of 3'-UTR is responsible for the translational inhibition. RNA stability experiment reveals that the AU-rich segment leads to a 3-fold decrease of t-PA mRNA stability. The insertion of this segment into the 3'-UTR of luciferase gene results in an obvious inhibition of Luc expression. A model is proposed for the regulation of t-PA expression.
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PMID:Inhibitory effect of 3'-untranslated region (3'-UTR) of human tissue-plasminogen activator (ht-PA) mRNA on its expression. 855 75

In mouse oocytes, tissue-type plasminogen activator (tPA) mRNA is under translational control. The newly transcribed mRNA undergoes deadenylation and translational silencing in growing oocytes, while readenylation and translation occur during meiotic maturation. To localize regulatory elements controlling tPA mRNA expression, we identified regions of the endogenous transcript protected from hybridization with injected antisense oligodeoxynucleotides. Most of the targeted sequences in either the 5' untranslated region (5'UTR), coding region, or 3'UTR were accessible to hybridization, as revealed by inhibition of tPA synthesis and by RNase protection. Two protected regions were identified in the 3'UTR of tPA mRNA in primary oocytes: the adenylation control element (ACE) and the AAUAAA polyadenylation signal. These sequences were previously shown to be involved in the translational control of injected reporter transcripts. During the first hour of meiotic maturation, part of the ACE and the AAUAAA hexanucleotide became accessible to hybridization, suggesting a partial unmasking of the 3'UTR of this mRNA before it becomes translationally competent. Our results demonstrate that in vivo antisense oligodeoxynucleotide mapping can reveal the dynamics of regulatory features of a native mRNA in the context of the intact cell. They suggest that specific regions in the 3'UTR of tPA mRNA function as cis-acting masking determinants involved in the silencing of tPA mRNA in primary oocytes.
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PMID:In vivo antisense oligodeoxynucleotide mapping reveals masked regulatory elements in an mRNA dormant in mouse oocytes. 912 23

The mechanisms responsible for translational silencing of certain mRNAs in growing oocytes, and for their awakening during meiotic maturation, are not completely elucidated. We show that binding of a approximately 80-kD protein to a UA-rich element in the 3' UTR of tissue-type plasminogen activator mRNA, a mouse oocyte mRNA that is translated during meiotic maturation, silences the mRNA in primary oocytes. Translation can be triggered by injecting a competitor transcript that displaces this silencing factor, without elongation of a pre-existing short poly(A) tail, the presence of which is mandatory. During meiotic maturation, cytoplasmic polyadenylation is necessary to maintain a poly(A) tail, but the determining event for translational activation appears to be the modification or displacement of the silencing factor.
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PMID:Masking, unmasking, and regulated polyadenylation cooperate in the translational control of a dormant mRNA in mouse oocytes. 971 6

We have generated a mouse strain carrying a transgene driven by a strong and ubiquitous promoter (human cytomegalovirus hCMV/beta-actin) and containing an enhanced green fluorescent protein (eGFP) coding sequence upstream of the 3' untranslated region (3'UTR) of tissue-type plasminogen activator (t-PA) mRNA. The 3'UTR of t-PA mRNA is known to be involved in the reversible deadenylation and translational repression of transcripts in mouse oocytes. hCMV/beta-actin-eGFP-3'UTR t-PA transgenic mice express eGFP mRNA in all brain structures analyzed but lack eGFP fluorescence, with the exception of blood vessels, choroid plexus, and Purkinje cells. Taking advantage of these features, we tested whether certain pathological conditions, in particular injuries of the nervous system, might trigger eGFP fluorescence in traumatized cells or neurons. From this perspective, we analyzed eGFP mRNA expression and eGFP fluorescence in experimental models of nervous system lesions, such as motoneuron axotomy and cerebral stroke induced by middle cerebral artery occlusion. We found an increase in eGFP fluorescence in specific brain areas in cells suffering or reacting to these injuries. This increased fluorescence is correlated with an increased transcription of eGFP in lesioned cells, presumably enhanced by a release of the translational silencing mediated by the 3'UTR region of the t-PA mRNA. This transgenic mouse model may prove useful to study the development of neurodegenerative lesions.
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PMID:Induction of enhanced green fluorescent protein expression in response to lesions in the nervous system. 1515 81

The proteinase inhibitor, type-1 plasminogen activator inhibitor (PAI-1), is a major regulator of the plasminogen activator system involved in plasmin formation and fibrinolysis. The present study explores the effects of intracellular iron on the expression of PAI-1 and associated cell-surface plasmin activity in human lung fibroblasts; and reports the presence of a novel iron-responsive protein. ELISA revealed a dose-dependent increase in PAI-1 antigen levels expressed in the conditioned medium of cells treated with deferoxamine, in the three cell lines studied. A concomitant increase in mRNA levels was also observed by Northern analyses. Presaturation with ferric citrate quenched the effect of deferoxamine. Experiments with transcription and translation inhibitors on TIG 3-20 cells demonstrated that intracellular iron modulated PAI-1 expression at the post-transcriptional level with the requirement of de-novo protein synthesis. Electrophoretic mobility shift assay and UV crosslinking assays revealed the presence of an approximately 81-kDa nuclear protein that interacted with the 3'-UTR of PAI-1 mRNA in an iron-sensitive manner. Finally, we demonstrated that the increased PAI-1 is functional in suppressing cell-surface plasmin activity, a process that can affect wound healing and tissue remodeling.
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PMID:Post-transcriptional regulation of plasminogen activator inhibitor-1 by intracellular iron in cultured human lung fibroblasts--interaction of an 81-kDa nuclear protein with the 3'-UTR. 1586 97

During oogenesis, mRNA is actively transcribed and accumulated in growing oocytes, but this transcription stops before the oocytes grow to their full size. The accumulated maternal mRNA is used for protein synthesis in the oocytes during meiotic maturation and even in the embryos to sustain development after fertilization. Therefore, the degradation of accumulated maternal mRNA starts during meiotic maturation, but its rate is slow. Nevertheless, some mRNA species should rapidly degrade after fertilization if they encode proteins that play a role in specific events during meiosis and are detrimental for development after fertilization. In this study, to identify the selective degradation of maternal transcripts after fertilization, we sought mRNAs that are degraded in the early hours after fertilization by constructing an oocyte cDNA library after subtracting the cDNA of embryos at the mid one-cell stage. H1oo, c-mos, tPA (tissue type plasminogen activator gene), and Gdf9 were identified as genes whose transcripts undergo rapid degradation after fertilization. RT-PCR analysis showed that none of these transcripts was expressed during pre-implantation development once they were eliminated, suggesting that the mRNA species that are required for oogenesis, but not for early pre-implantation development, are degraded rapidly after fertilization. Microinjection of chimeric mRNAs in which the coding and 3'-untranslated regions (3'UTR) were exchanged between c-mos and hypoxanthine phosphoribosyltransferase mRNAs revealed that the 3'UTR plays a role in the rapid degradation that occurs after fertilization. Cytoplasmic polyadenylation elements (CPEs) was found near a poly(A) signal in the 3'UTR of all the mRNA species identified as rapidly degrading mRNA. The mechanism for the selective degradation is discussed, in relation to its biological significance.
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PMID:Degradation of maternal mRNA in mouse embryos: selective degradation of specific mRNAs after fertilization. 1609 46

Two serine proteases, urokinase and tissue type, control the activation of plasminogen to plasmin. These proteases are in turn specifically inhibited by plasminogen activator inhibitors type 1 and 2 (PAI-1 and PAI-2), both of which belong to the serine protease inhibitor (serpin) superfamily. Very little information is available on the role of PAI-1 and PAI-2 in ruminants, in mammary gland involution and in the adipose tissue. In this paper we describe the isolation of the full-length cDNAs of ovine PAI-1 and PAI-2 using a polymerase chain reaction based strategy. The ovine PAI-1 cDNA comprised of 1460bp and it is characterized by a coding region of 1209bp, and 5'- and 3'-UTR regions of 147 and 104bp, respectively. The deduced amino acid sequence consists of 402 amino acids. The ovine PAI-2 cDNA is comprised of 2128bp and it is characterized by a coding region of 957bp and 5'- and 3'-UTR regions of 58 and 819bp respectively. The deduced amino acid sequence consists of 416 amino acids. Three-dimensional models of the putative protein products of both cDNAs showed that the proteins bear a high similarity with their human counterparts. Real-time PCR revealed that the two inhibitors were predominantly expressed in the ovine mammary gland and adipose tissue. Furthermore, PAI-1 and PAI-2 mRNA levels were higher in the involuting mammary tissue and the adipose tissue obtained from non-lactating ewes compared to the corresponding values in tissues obtained from lactating ewes. These data are consistent with the notion that the plasminogen activation cascade plays a key role in involution of the mammary gland. The upregulation of expression of both inhibitors in the adipose tissue during the non-lactating period is a rather enigmatic observation. However, the expression of both inhibitors (PAI-1 and PAI-2) together with that of urokinase type plasminogen activator and its receptor previously reported by our group, strengthen the suggestion that the adipose tissue functions as an endocrine besides an energy storage organ.
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PMID:The ovine plasminogen activator inhibitors type 1 and type 2 cDNAs: molecular cloning, characterization and expression in various tissues. 2011 71