Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human inducible NO synthase (iNOS) expression is regulated by post-transcriptional mechanisms. The 3'-untranslated region (3'-UTR) of the human iNOS mRNA contains AU-rich elements (ARE), which are known to be important for the regulation of mRNA stability. The 3'-UTR of the human iNOS mRNA has been shown to regulate human iNOS mRNA expression post-transcriptionally. One RNA-binding protein known to interact with AREs and to regulate mRNA stability is the T cell intracellular antigen-1-related protein (TIAR). In RNA binding studies TIAR displayed high affinity binding to the human iNOS 3'-UTR sequence. In RNase protection experiments, the cytokine incubation needed for iNOS expression did not change TIAR expression in DLD-1 cells. However, overexpression of TIAR in human DLD-1 colon carcinoma cells resulted in enhanced cytokine-induced iNOS expression. In conclusion, TIAR seems to be involved in the post-transcriptional regulation of human iNOS expression.
...
PMID:The RNA binding protein TIAR is involved in the regulation of human iNOS expression. 1619 98

The 3'-UTR (untranslated region) of bcl-2 mRNA contains an ARE (AU-rich element) that potentially regulates the stability of bcl-2 mRNA in a cell specific fashion. Previous studies have demonstrated that multiple proteins interact with bcl-2 mRNA in HL-60 (human leukaemia-60) cells, potentially contributing to the overexpression of Bcl-2 protein. Treatment of HL-60 cells with taxol or okadaic acid has been shown to induce destabilization of bcl-2 mRNA, which was associated with decreased binding of trans-acting factors to bcl-2 mRNA. Nucleolin has been identified as one of the bcl-2 mRNA-binding proteins [Sengupta, Bandyopadhyay, Fernandes and Spicer (2004) J. Biol. Chem. 279, 10855-10863]. In an effort to identify additional bcl-2 mRNA-binding proteins, two polypeptides of approx. 45 kDa and 60 kDa were isolated from HL-60 cells by ARE(bcl-2) (transcripts that contain bcl-2 AREs) RNA affinity chromatography. These proteins were identified as the human proliferation associated protein, Ebp1, and human DRBP76 (double stranded RNA-binding protein 76) respectively, by MALDI (matrix-assisted laser-desorption ionization)-MS. RNA electrophoretic mobility shift assays indicated that recombinant Ebp1 binds to ARE(bcl-2) RNA but not to the group 1 ARE present in GM-CSF (granulocyte macrophage-colony stimulating factor) mRNA in vitro. Antibody supershift assays demonstrated that Ebp1 is present in protein-ARE(bcl-2) RNA complexes formed with cytosolic HL-60 extracts. The interaction of Ebp1 with bcl-2 mRNA in HL-60 cells was also demonstrated by RNA co-immunoprecipitation assays. This interaction was not detected in extracts of taxol-treated HL-60 cells. Immunoprecipitation assays further revealed that Ebp1 co-precipitates with nucleolin from HL-60 cytoplasmic extracts. The observation that co-precipitation was decreased when extracts were treated with RNase suggests that Ebp1 and nucleolin are present in the same bcl-2 mRNP (messenger ribonucleoprotein particle) complexes. RNA-decay assays further demonstrated that Ebp1 decreased the rate of decay of beta-globin-ARE(bcl-2) transcripts in HL-60 cell extracts. Collectively, these results indicate a novel function for Ebp1 in contributing to the regulation of bcl-2 expression in HL-60 cells.
...
PMID:Identification of Ebp1 as a component of cytoplasmic bcl-2 mRNP (messenger ribonucleoprotein particle) complexes. 1639 31

The hepatitis C virus (HCV) core protein is involved in the assembly of nucleocapsid particles, as well as regulation of cellular and viral gene expression. To investigate the biological properties of the viral core protein and viral RNA assembly, two recombinant core proteins, the mature core protein (named C179) and a C-terminal truncated protein (named C124), were expressed and purified. To confirm their ability to generate viral particles, the production of nucleocapsid-like particles was monitored using transmission electron microscopy (EM). The EM analysis revealed that exposure of these proteins to the 5' untranslated region (5' UTR) of the viral RNA resulted in generation of spherical particles of 30-140nm in diameter. Interestingly, a cross-linking analysis revealed that C124 required an RNA component for homotypic interactions. In contrast, C179 successfully assembled in the absence of nucleic acids. Additionally, RNA-mediated conversion of the C124 structure into a more stable state was maintained even after RNase treatment. Therefore, our results indicate that the basic N-terminal domain of the viral core protein utilizes RNA components to induce conformational changes or efficient homotypic interactions, while the C-terminal domain may contain key peptide sequences for initiating spontaneous multimerization at the early stages of viral assembly.
...
PMID:Structural requirements for assembly and homotypic interactions of the hepatitis C virus core protein. 1694 99

RNase-L mediates critical cellular functions including antiviral, pro-apoptotic, and tumor suppressive activities; accordingly, its expression must be tightly regulated. Little is known about the control of RNASEL expression; therefore, we examined the potential regulatory role of a conserved 3'-untranslated region (3'-UTR) in its mRNA. The 3'-UTR mediated a potent decrease in the stability of RNase-L mRNA, and of a chimeric beta-globin-3'-UTR reporter mRNA. AU-rich elements (AREs) are cis-acting regulatory regions that modulate mRNA stability. Eight AREs were identified in the RNase-L 3'-UTR, and deletion analysis identified positive and negative regulatory regions associated with distinct AREs. In particular, AREs 7 and 8 served a strong positive regulatory function. HuR is an ARE-binding protein that stabilizes ARE-containing mRNAs, and a predicted HuR binding site was identified in the region comprising AREs 7 and 8. Co-transfection of HuR and RNase-L enhanced RNase-L expression and mRNA stability in a manner that was dependent on this 3'-UTR region. Immunoprecipitation demonstrated that RNase-L mRNA associates with a HuR containing complex in intact cells. Activation of endogenous HuR by cell stress, or during myoblast differentiation, increased RNase-L expression, suggesting that RNase-L mRNA is a physiologic target for HuR. HuR-dependent regulation of RNase-L enhanced its antiviral activity demonstrating the functional significance of this regulation. These findings identify a novel mechanism of RNase-L regulation mediated by its 3'-UTR.
...
PMID:Post-transcriptional regulation of RNase-L expression is mediated by the 3'-untranslated region of its mRNA. 1723 28

The multifunctional proteins aldolase C and poly (A)-binding protein (PABP) undergo competitive interactions in cells coexpressing aldolase C and NF-L. A specific in vivo interaction between aldolase C and NF-L mRNA had been localized to a 68 nt segment of the transcript spanning the translation termination signal. It is shown here that the poly (A)-binding protein (PABP) binds the body of the NF-L transcript and increases its levels of expression when an excess of PABP is transiently provided in trans. Immunoprecipitation of PABP-associated ribonucleoprotein complexes of human spinal cord pulls down the dimeric form of aldolase C suggesting that their co-regulation of NF-L expression could be linked to the oligomerization status of aldolase C. An ex vivo model of mRNA decay has assessed mechanisms whereby aldolase C and PABP control NF-L expression. This model shows that aldolase C is a zinc-activated ribonuclease that cleaves the transcript at sites closed to the end-terminal structures. Immunological and biochemical depletion of endogenous PABP increases the instability of the transcript suggesting that PABP shields the NF-L mRNA from aldolase attack. An in vitro model shows that a mutant NF-L 68, in which the 45 nt of proximal 3'-UTR is replaced with unrelated sequence, is not degraded by aldolase C. Taken together, the findings might have important consequences for understanding causal mechanisms underlying neurodegeneration.
...
PMID:Coregulation of light neurofilament mRNA by poly(A)-binding protein and aldolase C: implications for neurodegeneration. 1727 15

We previously demonstrated that Paracentrotus lividus Hsp56 mitochondrial chaperonin is constitutively expressed during development, that it has a specific territorial distribution, both in normal and heat-shocked embryos, and that its amount increases after heat shock [Roccheri MC, Patti M, Agnello M, Gianguzza F, Carra E, Rinaldi AM. Localization of mitochondrial Hsp56 chaperonin during sea urchin development. Biochem Biophys Res Commun 2001;287:1093-98] and cadmium treatment [Roccheri MC, Agnello M, Boneventura R, Matranga V. Cadmium induces the expression of specific stress proteins in sea urchin embryos. Biochem Biophys Res Commun 2004;321:80-7]. In this study, we looked at Hsp56 mRNA during normal development and under stress conditions. The messenger is almost constantly expressed at all stages of development and its amount is steadily increased in stressed embryos. Moreover, we found, using T1 RNase protection assay, that the most proximal region of the 3'-UTR of the Hsp56 mRNA binds a 40 kDa protein: this factor is more abundant in the mitochondrial extract and, more specifically, in the outer membrane of the organelle.
...
PMID:Hsp56 mRNA in Paracentrotus lividus embryos binds to a mitochondrial protein. 1758 6

Several recent publications have explored cap-independent translation through an internal ribosome entry site (IRES) in the 5'-UTR of the mRNA encoding the cyclin-dependent kinase inhibitor p27. The major experimental tool used in these reports was the use of bicistronic reporter constructs in which the 5'-UTR was inserted between the upstream and downstream cistrons. None of these reports has completely ruled out the possibility that the 5'-UTR has either cryptic promoter activity or a cryptic splice acceptor site. Either of these possibilities could result in expression of a monocistronic mRNA encoding the downstream cistron and false identification of an IRES. Indeed, Liu et al. recently published data suggesting that the p27 5'-UTR harbors cryptic promoter activity which accounts for its putative IRES activity. In this report, we have explored this potential problem further using promoterless bicistronic constructs coupled with RNase protection assays, siRNA knockdown of individual cistrons, RT-PCR to detect mRNA encoded by the bicistronic reporter with high sensitivity, direct transfection of bicistronic mRNAs, and insertion of an iron response element into the bicistronic reporter. The results do not support the conclusion that the p27 5'-UTR has significant functional promoter activity or cryptic splice sites, but rather that it is able to support cap-independent initiation of translation.
...
PMID:Cap-independent translation through the p27 5'-UTR. 1761 41

The life cycle of Leishmania alternates between developmental forms residing within the insect vector (e.g. promastigotes) and the mammalian host (amastigotes). In Leishmania nearly all control of gene expression is post-transcriptional and involves sequences in the 3'-untranslated regions (3'UTRs) of mRNAs. Very little is known as to how these cis-elements regulate RNA turnover and translation rates in trypanosomatids and nothing is known about mRNA degradation mechanisms in Leishmania in particular. Here, we use the amastin mRNA-an amastigote-specific transcript-as a model and show that a approximately 100 nt U-rich element (URE) within its 3'UTR significantly accounts for developmental regulation. RNase-H-RNA blot analysis revealed that a major part of the rapid promastigote-specific degradation of the amastin mRNA is not initiated by deadenylation. This is in contrast to the amastin mRNA in amastigotes and to reporter RNAs lacking the URE, which, in common with most eukaryotic mRNAs studied to-date, are deadenylated before being degraded. Moreover, our analysis did not reveal a role for decapping in the stage-specific degradation of the amastin mRNA. Overall, these results suggest that degradation of the amastin mRNA of Leishmania is likely to be bi-phasic, the first phase being stage-specific and dependent on an unusual URE-mediated pathway of mRNA degradation.
...
PMID:Deadenylation-independent stage-specific mRNA degradation in Leishmania. 1825 85

Adipose LPL (lipoprotein lipase) plays an important role in regulating plasma triacylglycerols and lipid metabolism. We have previously demonstrated that PKCalpha (protein kinase Calpha) depletion inhibits LPL translation in 3T3-F442A adipocytes. Using in vitro translation experiments, the minimum essential region on the 3'UTR (3'-untranslated region) of LPL mRNA required for the inhibition of translation was identified as the proximal 39 nt. These results were confirmed by RNase protection analysis using cytoplasmic proteins isolated from the adipocytes treated with PKCalpha antisense oligomers and the LPL 3'UTR transcript (LPL 3'UTR nt: 1512-1640). The protein components involved in this RNA-binding interaction from PKCalpha depletion were passed through an affinity column containing a sequence of the LPL 3'UTR and, after Western blotting, the RNA-binding proteins were identified as the catalytic and the regulatory subunits of PKA (protein kinase A), Calpha and RIIbeta, and AKAP (A-kinase-anchoring protein) 121. This RNA inhibitory complex consisted of the same RNA-binding proteins that have been identified previously as mediators of LPL translational inhibition by PKA activation, suggesting that PKCalpha depletion inhibits LPL translation through PKA activation. In additional experiments, PKC depletion by prolonged PMA treatment or PKCalpha antisense oligomers resulted in an increase in PKA activity in 3T3-F442A adipocytes, comparable with PKA activation with adrenaline (epinephrine) treatment. These results demonstrate that LPL translational inhibition occurs through an RNA-binding complex involving PKA subunits and AKAP121, and this complex can be activated either through traditional PKA activation methods or through the depletion of PKCalpha.
...
PMID:Translational regulation of lipoprotein lipase in adipocytes: depletion of cellular protein kinase Calpha activates binding of the C subunit of protein kinase A to the 3'-untranslated region of the lipoprotein lipase mRNA. 1838 1

Cc RNase is the founding member of the recently identified RNase kappa family, which is represented by a single ortholog in a wide range of animal taxonomic groups. Although the precise biological role of this protein is still unknown, it has been shown that the recombinant proteins isolated so far from the insect Ceratitis capitata and from human exhibit ribonucleolytic activity. In this work, we report the genomic organization and molecular evolution of the RNase kappa gene from various animal species, as well as expression analysis of the ortholog gene in C. capitata. The high degree of amino acid sequence similarity, in combination with the fact that exon sizes and intronic positions are extremely conserved among RNase kappa orthologs in 15 diverse genomes from sea anemone to human, imply a very significant biological function for this enzyme. In C. capitata, two forms of RNase kappa mRNA (0.9 and 1.5 kb) with various lengths of 3' UTR were identified as alternative products of a single gene, resulting from the use of different polyadenylation signals. Both transcripts are expressed in all insect tissues and developmental stages. Sequence analysis of the extended region of the longer transcript revealed the existence of three mRNA instability motifs (AUUUA) and five poly(U) tracts, whose functional importance in RNase kappa mRNA decay remains to be explored.
...
PMID:Genomic structure and expression analysis of the RNase kappa family ortholog gene in the insect Ceratitis capitata. 1901 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---