FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1964592036> ?p ?o ?g. }

• W1964592036 endingPage "2407" @default.
• W1964592036 startingPage "2401" @default.
• W1964592036 abstract "Iron regulatory proteins (IRPs) control the synthesis of several proteins in iron metabolism by binding to iron-responsive elements (IREs), a hairpin structure in the untranslated region (UTR) of corresponding mRNAs. Binding of IRPs to IREs in the 5′ UTR inhibits translation of ferritin heavy and light chain, erythroid aminolevulinic acid synthase, mitochondrial aconitase, and Drosophila succinate dehydrogenase b, whereas IRP binding to IREs in the 3′ UTR of transferrin receptor mRNA prolongs mRNA half-life. To identify new targets of IRPs, we devised a method to enrich IRE-containing mRNAs by using recombinant IRP-1 as an affinity matrix. A cDNA library established from enriched mRNA was screened by an RNA-protein band shift assay. This revealed a novel IRE-like sequence in the 3′ UTR of a liver-specific mouse mRNA. The newly identified cDNA codes for a protein with high homology to plant glycolate oxidase (GOX). Recombinant protein expressed in bacteria displayed enzymatic GOX activity. Therefore, this cDNA represents the first vertebrate GOX homologue. The IRE-like sequence in mouse GOX exhibited strong binding to IRPs at room temperature. However, it differs from functional IREs by a mismatch in the middle of its upper stem and did not confer iron-dependent regulation in cells. Iron regulatory proteins (IRPs) control the synthesis of several proteins in iron metabolism by binding to iron-responsive elements (IREs), a hairpin structure in the untranslated region (UTR) of corresponding mRNAs. Binding of IRPs to IREs in the 5′ UTR inhibits translation of ferritin heavy and light chain, erythroid aminolevulinic acid synthase, mitochondrial aconitase, and Drosophila succinate dehydrogenase b, whereas IRP binding to IREs in the 3′ UTR of transferrin receptor mRNA prolongs mRNA half-life. To identify new targets of IRPs, we devised a method to enrich IRE-containing mRNAs by using recombinant IRP-1 as an affinity matrix. A cDNA library established from enriched mRNA was screened by an RNA-protein band shift assay. This revealed a novel IRE-like sequence in the 3′ UTR of a liver-specific mouse mRNA. The newly identified cDNA codes for a protein with high homology to plant glycolate oxidase (GOX). Recombinant protein expressed in bacteria displayed enzymatic GOX activity. Therefore, this cDNA represents the first vertebrate GOX homologue. The IRE-like sequence in mouse GOX exhibited strong binding to IRPs at room temperature. However, it differs from functional IREs by a mismatch in the middle of its upper stem and did not confer iron-dependent regulation in cells. iron regulatory protein glycolate oxidase glutathioneS-transferase human growth hormone iron-responsive element untranslated region succinate dehydrogenase b heavy light. RNA-binding proteins play a central role in RNA processing, nucleo-cytoplasmic transport, localization, translation, or stability. This makes it desirable to identify all the targets of a given RNA-binding protein. Because many RNA recognition elements cannot be identified by hybridization or predicted with certainty by search programs, we developed an experimental approach based on the interaction between an RNA-binding protein and its target RNAs. As a model system we are investigating the iron regulatory proteins 1 and 2 (IRP-1 and IRP-2),1 which become active in iron-deprived cells and bind with high affinity to structural RNA motifs, the iron-responsive elements (IREs) (1Leibold E.A. Munro H.N. Proc. Natl Acad. Sci. U. S. A. 1988; 85: 2171-2175Crossref PubMed Scopus (554) Google Scholar, 2Casey J.L. Hentze M.W. Koeller D.M. Caughman S.W. Rouault T.A. Klausner R.D. Harford J.B. Science. 1988; 240: 924-928Crossref PubMed Scopus (506) Google Scholar, 3Müllner E.W. Neupert B. Kühn L.C. Cell. 1989; 58: 373-382Abstract Full Text PDF PubMed Scopus (401) Google Scholar, 4Haile D.J. Hentze M.W. Rouault T.A. Harford J.B. Klausner R.D. Mol. Cell. Biol. 1989; 9: 5055-5061Crossref PubMed Google Scholar, 5Barton H.A. Eisenstein R.S. Bomford A. Munro H.N. J. Biol. Chem. 1990; 265: 7000-7008Abstract Full Text PDF PubMed Google Scholar). IRPs repress translation of mRNAs with a cap-proximal IRE, as found in the mRNA of ferritin heavy (H) and light (L) chain (1Leibold E.A. Munro H.N. Proc. Natl Acad. Sci. U. S. A. 1988; 85: 2171-2175Crossref PubMed Scopus (554) Google Scholar, 6Hentze M.W. Caughman S.W. Rouault T.A. Barriocanal J.G. Dancis A. Harford J.B. Klausner R.D. Science. 1987; 238: 1570-1573Crossref PubMed Scopus (387) Google Scholar), mitochondrial aconitase (7Zheng L. Kennedy M.C. Blondin G.A. Beinert H. Zalkin H. Arch. Biochem. Biophys. 1992; 299: 356-360Crossref PubMed Scopus (66) Google Scholar, 8Gray N.K. Pantopoulous K. Dandekar T. Ackrell B.A. Hentze M.W. Proc. Natl Acad. Sci. U. S. A. 1996; 93: 4925-4930Crossref PubMed Scopus (164) Google Scholar), erythroid 5-aminolevulinic acid synthase (9Cox T.C. Bawden M.J. Martin A. May B.K. EMBO J. 1991; 10: 1891-1902Crossref PubMed Scopus (304) Google Scholar, 10Dandekar T. Stripecke R. Gray N.K. Goossen B. Constable A. Johansson H.E. Hentze M.W. EMBO J. 1991; 10: 1903-1909Crossref PubMed Scopus (275) Google Scholar), and Drosophila succinate dehydrogenase b (SDHb) (8Gray N.K. Pantopoulous K. Dandekar T. Ackrell B.A. Hentze M.W. Proc. Natl Acad. Sci. U. S. A. 1996; 93: 4925-4930Crossref PubMed Scopus (164) Google Scholar, 11Kohler S.A. Henderson B.R. Kühn L.C. J. Biol. Chem. 1995; 270: 30781-30786Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 12Melefors Ö. Biochem. Biophys. Res. Commun. 1996; 221: 437-441Crossref PubMed Scopus (45) Google Scholar). As a consequence, IRP binding lowers iron storage and utilization. Moreover, binding of IRPs to five IREs in the 3′ untranslated region (UTR) of transferrin receptor mRNA protects this otherwise unstable mRNA from degradation (3Müllner E.W. Neupert B. Kühn L.C. Cell. 1989; 58: 373-382Abstract Full Text PDF PubMed Scopus (401) Google Scholar, 13Koeller D.M. Casey J.L. Hentze M.W. Gerhardt E.M. Chan L.N. Klausner R.D. Harford J.B. Proc. Natl Acad. Sci. U. S. A. 1989; 86: 3574-3578Crossref PubMed Scopus (176) Google Scholar). This leads to more receptor synthesis and enhanced iron uptake.Functional IREs form stem loop structures with a conserved CAGUGN loop sequence (where N is any nucleotide except G). An upper stem of five perfectly paired bases is separated from a lower stem by a single cytosine on the 5′ side or by a cytosine preceded by two nucleotides with one unpaired nucleotide on the 3′ side. Adopting an in vitro selection procedure, we and others have identified IREs with alternative loop sequences that bind to IRPs and of which some show a preferential interaction with IRP-1 or IRP-2 (14Henderson B.R. Menotti E. Bonnard C. Kühn L.C. J. Biol. Chem. 1994; 269: 17481-17489Abstract Full Text PDF PubMed Google Scholar, 15Butt J. Kim H.Y. Basilion J.P. Cohen S. Iwai K. Philpott C.C. Altschul S. Klausner R.D. Rouault T.A. Proc. Natl Acad. Sci. U. S. A. 1996; 93: 4345-4349Crossref PubMed Scopus (129) Google Scholar, 16Henderson B.R. Menotti E. Kühn L.C. J. Biol. Chem. 1996; 271: 4900-4908Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar). Such IRE mutants confer translational control in vivo when inserted into the 5′ UTR of a reporter construct (17Menotti E. Henderson B.R. Kühn L.C. J. Biol. Chem. 1998; 273: 1821-1824Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar). However, none of these alternative IREs was detected in naturally occurring mRNAs to date.Here we devised a method to enrich IRE-containing mRNAs by using recombinant human IRP-1 as an affinity matrix (Fig. 1). We then constructed an enriched cDNA library from mouse liver mRNA and screened it for IREs by RNA-protein band shift assays. This revealed a clone with strong homology to plant glycolate oxidase (GOX, or short-chain α-hydroxy acid oxidase, EC 1.1.3.15). In plants, this enzyme participates in the glyoxylate cycle and catalyzes the oxidation of glycolate to glyoxylate. An IRE-like sequence was found in the 3′ UTR of the mouse mRNA and analyzed with respect to its possible involvement in iron-dependent, post-transcriptional regulation. RNA-binding proteins play a central role in RNA processing, nucleo-cytoplasmic transport, localization, translation, or stability. This makes it desirable to identify all the targets of a given RNA-binding protein. Because many RNA recognition elements cannot be identified by hybridization or predicted with certainty by search programs, we developed an experimental approach based on the interaction between an RNA-binding protein and its target RNAs. As a model system we are investigating the iron regulatory proteins 1 and 2 (IRP-1 and IRP-2),1 which become active in iron-deprived cells and bind with high affinity to structural RNA motifs, the iron-responsive elements (IREs) (1Leibold E.A. Munro H.N. Proc. Natl Acad. Sci. U. S. A. 1988; 85: 2171-2175Crossref PubMed Scopus (554) Google Scholar, 2Casey J.L. Hentze M.W. Koeller D.M. Caughman S.W. Rouault T.A. Klausner R.D. Harford J.B. Science. 1988; 240: 924-928Crossref PubMed Scopus (506) Google Scholar, 3Müllner E.W. Neupert B. Kühn L.C. Cell. 1989; 58: 373-382Abstract Full Text PDF PubMed Scopus (401) Google Scholar, 4Haile D.J. Hentze M.W. Rouault T.A. Harford J.B. Klausner R.D. Mol. Cell. Biol. 1989; 9: 5055-5061Crossref PubMed Google Scholar, 5Barton H.A. Eisenstein R.S. Bomford A. Munro H.N. J. Biol. Chem. 1990; 265: 7000-7008Abstract Full Text PDF PubMed Google Scholar). IRPs repress translation of mRNAs with a cap-proximal IRE, as found in the mRNA of ferritin heavy (H) and light (L) chain (1Leibold E.A. Munro H.N. Proc. Natl Acad. Sci. U. S. A. 1988; 85: 2171-2175Crossref PubMed Scopus (554) Google Scholar, 6Hentze M.W. Caughman S.W. Rouault T.A. Barriocanal J.G. Dancis A. Harford J.B. Klausner R.D. Science. 1987; 238: 1570-1573Crossref PubMed Scopus (387) Google Scholar), mitochondrial aconitase (7Zheng L. Kennedy M.C. Blondin G.A. Beinert H. Zalkin H. Arch. Biochem. Biophys. 1992; 299: 356-360Crossref PubMed Scopus (66) Google Scholar, 8Gray N.K. Pantopoulous K. Dandekar T. Ackrell B.A. Hentze M.W. Proc. Natl Acad. Sci. U. S. A. 1996; 93: 4925-4930Crossref PubMed Scopus (164) Google Scholar), erythroid 5-aminolevulinic acid synthase (9Cox T.C. Bawden M.J. Martin A. May B.K. EMBO J. 1991; 10: 1891-1902Crossref PubMed Scopus (304) Google Scholar, 10Dandekar T. Stripecke R. Gray N.K. Goossen B. Constable A. Johansson H.E. Hentze M.W. EMBO J. 1991; 10: 1903-1909Crossref PubMed Scopus (275) Google Scholar), and Drosophila succinate dehydrogenase b (SDHb) (8Gray N.K. Pantopoulous K. Dandekar T. Ackrell B.A. Hentze M.W. Proc. Natl Acad. Sci. U. S. A. 1996; 93: 4925-4930Crossref PubMed Scopus (164) Google Scholar, 11Kohler S.A. Henderson B.R. Kühn L.C. J. Biol. Chem. 1995; 270: 30781-30786Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 12Melefors Ö. Biochem. Biophys. Res. Commun. 1996; 221: 437-441Crossref PubMed Scopus (45) Google Scholar). As a consequence, IRP binding lowers iron storage and utilization. Moreover, binding of IRPs to five IREs in the 3′ untranslated region (UTR) of transferrin receptor mRNA protects this otherwise unstable mRNA from degradation (3Müllner E.W. Neupert B. Kühn L.C. Cell. 1989; 58: 373-382Abstract Full Text PDF PubMed Scopus (401) Google Scholar, 13Koeller D.M. Casey J.L. Hentze M.W. Gerhardt E.M. Chan L.N. Klausner R.D. Harford J.B. Proc. Natl Acad. Sci. U. S. A. 1989; 86: 3574-3578Crossref PubMed Scopus (176) Google Scholar). This leads to more receptor synthesis and enhanced iron uptake. Functional IREs form stem loop structures with a conserved CAGUGN loop sequence (where N is any nucleotide except G). An upper stem of five perfectly paired bases is separated from a lower stem by a single cytosine on the 5′ side or by a cytosine preceded by two nucleotides with one unpaired nucleotide on the 3′ side. Adopting an in vitro selection procedure, we and others have identified IREs with alternative loop sequences that bind to IRPs and of which some show a preferential interaction with IRP-1 or IRP-2 (14Henderson B.R. Menotti E. Bonnard C. Kühn L.C. J. Biol. Chem. 1994; 269: 17481-17489Abstract Full Text PDF PubMed Google Scholar, 15Butt J. Kim H.Y. Basilion J.P. Cohen S. Iwai K. Philpott C.C. Altschul S. Klausner R.D. Rouault T.A. Proc. Natl Acad. Sci. U. S. A. 1996; 93: 4345-4349Crossref PubMed Scopus (129) Google Scholar, 16Henderson B.R. Menotti E. Kühn L.C. J. Biol. Chem. 1996; 271: 4900-4908Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar). Such IRE mutants confer translational control in vivo when inserted into the 5′ UTR of a reporter construct (17Menotti E. Henderson B.R. Kühn L.C. J. Biol. Chem. 1998; 273: 1821-1824Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar). However, none of these alternative IREs was detected in naturally occurring mRNAs to date. Here we devised a method to enrich IRE-containing mRNAs by using recombinant human IRP-1 as an affinity matrix (Fig. 1). We then constructed an enriched cDNA library from mouse liver mRNA and screened it for IREs by RNA-protein band shift assays. This revealed a clone with strong homology to plant glycolate oxidase (GOX, or short-chain α-hydroxy acid oxidase, EC 1.1.3.15). In plants, this enzyme participates in the glyoxylate cycle and catalyzes the oxidation of glycolate to glyoxylate. An IRE-like sequence was found in the 3′ UTR of the mouse mRNA and analyzed with respect to its possible involvement in iron-dependent, post-transcriptional regulation. We thank Jovan Mirkovitch for the FTO2B cell line, Martin Irmler for carrying out the in vitrotranscription-translation experiment, and Markus Nabholz for critically reading the manuscript." @default.
• W1964592036 created "2016-06-24" @default.
• W1964592036 creator A5020891892 @default.
• W1964592036 creator A5059309295 @default.
• W1964592036 creator A5068992859 @default.
• W1964592036 date "1999-01-01" @default.
• W1964592036 modified "2023-10-18" @default.
• W1964592036 title "Molecular Cloning of Mouse Glycolate Oxidase" @default.
• W1964592036 cites W149801576 @default.
• W1964592036 cites W1511974550 @default.
• W1964592036 cites W1547848353 @default.
• W1964592036 cites W1556608266 @default.
• W1964592036 cites W1576283072 @default.
• W1964592036 cites W1584460159 @default.
• W1964592036 cites W1608904060 @default.
• W1964592036 cites W1965372133 @default.
• W1964592036 cites W1965557392 @default.
• W1964592036 cites W1973706463 @default.
• W1964592036 cites W1974106715 @default.
• W1964592036 cites W1979644010 @default.
• W1964592036 cites W1986492446 @default.
• W1964592036 cites W1990131534 @default.
• W1964592036 cites W1999347013 @default.
• W1964592036 cites W2009310436 @default.
• W1964592036 cites W2009834160 @default.
• W1964592036 cites W2010346856 @default.
• W1964592036 cites W2013297780 @default.
• W1964592036 cites W2015629167 @default.
• W1964592036 cites W2017204685 @default.
• W1964592036 cites W2018366596 @default.
• W1964592036 cites W2036382643 @default.
• W1964592036 cites W2045348184 @default.
• W1964592036 cites W2054884001 @default.
• W1964592036 cites W2058642246 @default.
• W1964592036 cites W2058913692 @default.
• W1964592036 cites W2073274737 @default.
• W1964592036 cites W2080400658 @default.
• W1964592036 cites W2082971144 @default.
• W1964592036 cites W2085062077 @default.
• W1964592036 cites W2085866164 @default.
• W1964592036 cites W2094794452 @default.
• W1964592036 cites W2099446928 @default.
• W1964592036 cites W2117403951 @default.
• W1964592036 cites W2160225986 @default.
• W1964592036 cites W2162573539 @default.
• W1964592036 cites W2162814004 @default.
• W1964592036 cites W2170566884 @default.
• W1964592036 cites W2231081458 @default.
• W1964592036 cites W2336704411 @default.
• W1964592036 cites W2398213076 @default.
• W1964592036 cites W27224777 @default.
• W1964592036 cites W299581075 @default.
• W1964592036 cites W32189543 @default.
• W1964592036 cites W4294216491 @default.
• W1964592036 cites W77941745 @default.
• W1964592036 cites W95648695 @default.
• W1964592036 doi "https://doi.org/10.1074/jbc.274.4.2401" @default.
• W1964592036 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9891009" @default.
• W1964592036 hasPublicationYear "1999" @default.
• W1964592036 type Work @default.
• W1964592036 sameAs 1964592036 @default.
• W1964592036 citedByCount "55" @default.
• W1964592036 countsByYear W19645920362012 @default.
• W1964592036 countsByYear W19645920362013 @default.
• W1964592036 countsByYear W19645920362014 @default.
• W1964592036 countsByYear W19645920362015 @default.
• W1964592036 countsByYear W19645920362016 @default.
• W1964592036 countsByYear W19645920362017 @default.
• W1964592036 countsByYear W19645920362018 @default.
• W1964592036 countsByYear W19645920362020 @default.
• W1964592036 countsByYear W19645920362022 @default.
• W1964592036 crossrefType "journal-article" @default.
• W1964592036 hasAuthorship W1964592036A5020891892 @default.
• W1964592036 hasAuthorship W1964592036A5059309295 @default.
• W1964592036 hasAuthorship W1964592036A5068992859 @default.
• W1964592036 hasBestOaLocation W19645920361 @default.
• W1964592036 hasConcept C104317684 @default.
• W1964592036 hasConcept C121050878 @default.
• W1964592036 hasConcept C153911025 @default.
• W1964592036 hasConcept C185592680 @default.
• W1964592036 hasConcept C187882448 @default.
• W1964592036 hasConcept C19924922 @default.
• W1964592036 hasConcept C199360897 @default.
• W1964592036 hasConcept C41008148 @default.
• W1964592036 hasConcept C54355233 @default.
• W1964592036 hasConcept C55493867 @default.
• W1964592036 hasConcept C70721500 @default.
• W1964592036 hasConcept C86803240 @default.
• W1964592036 hasConceptScore W1964592036C104317684 @default.
• W1964592036 hasConceptScore W1964592036C121050878 @default.
• W1964592036 hasConceptScore W1964592036C153911025 @default.
• W1964592036 hasConceptScore W1964592036C185592680 @default.
• W1964592036 hasConceptScore W1964592036C187882448 @default.
• W1964592036 hasConceptScore W1964592036C19924922 @default.
• W1964592036 hasConceptScore W1964592036C199360897 @default.
• W1964592036 hasConceptScore W1964592036C41008148 @default.
• W1964592036 hasConceptScore W1964592036C54355233 @default.
• W1964592036 hasConceptScore W1964592036C55493867 @default.

• next