Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in Mesenchymal Cells
ABSTRACT The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3′untranslated region (3′UTR) contains a highly conserved AU‐rich element (ARE) embedded in a sequence that commo...
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| Veröffentlicht in: | Journal of cellular biochemistry 2016-02, Vol.117 (2), p.439-447 |
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| creator | Fotinos, Anastasios Fritz, David T. Lisica, Steven Liu, Yijun Rogers, Melissa B. |
| description | ABSTRACT
The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3′untranslated region (3′UTR) contains a highly conserved AU‐rich element (ARE) embedded in a sequence that commonly represses gene expression in mesenchymal cells. Computational analyses indicate that this site also may bind several microRNAs (miRNAs). Although miRNAs frequently target AU‐rich regions, this ARE is unusual because the miRNAs directly span the ARE. We began to characterize the factors that may regulate Bmp2 expression via this complex site. The activating protein HuR (Hu antigen R, ELAVL1, HGNC:3312) directly binds this ARE and can activate gene expression. An miRNA was demonstrated to reverse HuR‐mediated activation. Mutational and RNA‐interference evidence also supports an AUF1 (AU‐factor‐1, HNRNPD, HGNC:5036) contribution to the observed repressive activity of the 3′UTR in mesenchymal cells. A limited number of studies describe how miRNAs interact with ARE‐binding proteins that bind adjacent sites. This study is among the first to describe protein/miRNA interactions at the same site. J. Cell. Biochem. 117: 439–447, 2016. © 2015 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/jcb.25290 |
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The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3′untranslated region (3′UTR) contains a highly conserved AU‐rich element (ARE) embedded in a sequence that commonly represses gene expression in mesenchymal cells. Computational analyses indicate that this site also may bind several microRNAs (miRNAs). Although miRNAs frequently target AU‐rich regions, this ARE is unusual because the miRNAs directly span the ARE. We began to characterize the factors that may regulate Bmp2 expression via this complex site. The activating protein HuR (Hu antigen R, ELAVL1, HGNC:3312) directly binds this ARE and can activate gene expression. An miRNA was demonstrated to reverse HuR‐mediated activation. Mutational and RNA‐interference evidence also supports an AUF1 (AU‐factor‐1, HNRNPD, HGNC:5036) contribution to the observed repressive activity of the 3′UTR in mesenchymal cells. A limited number of studies describe how miRNAs interact with ARE‐binding proteins that bind adjacent sites. This study is among the first to describe protein/miRNA interactions at the same site. J. Cell. Biochem. 117: 439–447, 2016. © 2015 Wiley Periodicals, Inc.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.25290</identifier><identifier>PMID: 26212702</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>3' Untranslated Regions ; Animals ; AU Rich Elements ; Base Sequence ; Binding, Competitive ; Bone Morphogenetic Protein 2 - genetics ; Bone Morphogenetic Protein 2 - metabolism ; Conserved Sequence ; ELAV-Like Protein 1 - metabolism ; GENE REGULATION ; GROWTH FACTOR ; HeLa Cells ; Heterogeneous-Nuclear Ribonucleoprotein D - genetics ; Heterogeneous-Nuclear Ribonucleoprotein D - metabolism ; Humans ; MESENCHYMAL CELL ; Mesenchymal Stromal Cells - metabolism ; Mice ; MicroRNAs - genetics ; Molecular Sequence Data ; POST-TRANSCRIPTIONAL ; RNA Interference</subject><ispartof>Journal of cellular biochemistry, 2016-02, Vol.117 (2), p.439-447</ispartof><rights>2015 Wiley Periodicals, Inc.</rights><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4800-3681d065575199476e5d41c7152b1cc002f006c50cd872a9c0b89cb27be7d48d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.25290$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.25290$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26212702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fotinos, Anastasios</creatorcontrib><creatorcontrib>Fritz, David T.</creatorcontrib><creatorcontrib>Lisica, Steven</creatorcontrib><creatorcontrib>Liu, Yijun</creatorcontrib><creatorcontrib>Rogers, Melissa B.</creatorcontrib><title>Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in Mesenchymal Cells</title><title>Journal of cellular biochemistry</title><addtitle>J. Cell. Biochem</addtitle><description>ABSTRACT
The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3′untranslated region (3′UTR) contains a highly conserved AU‐rich element (ARE) embedded in a sequence that commonly represses gene expression in mesenchymal cells. Computational analyses indicate that this site also may bind several microRNAs (miRNAs). Although miRNAs frequently target AU‐rich regions, this ARE is unusual because the miRNAs directly span the ARE. We began to characterize the factors that may regulate Bmp2 expression via this complex site. The activating protein HuR (Hu antigen R, ELAVL1, HGNC:3312) directly binds this ARE and can activate gene expression. An miRNA was demonstrated to reverse HuR‐mediated activation. Mutational and RNA‐interference evidence also supports an AUF1 (AU‐factor‐1, HNRNPD, HGNC:5036) contribution to the observed repressive activity of the 3′UTR in mesenchymal cells. A limited number of studies describe how miRNAs interact with ARE‐binding proteins that bind adjacent sites. This study is among the first to describe protein/miRNA interactions at the same site. J. Cell. Biochem. 117: 439–447, 2016. © 2015 Wiley Periodicals, Inc.</description><subject>3' Untranslated Regions</subject><subject>Animals</subject><subject>AU Rich Elements</subject><subject>Base Sequence</subject><subject>Binding, Competitive</subject><subject>Bone Morphogenetic Protein 2 - genetics</subject><subject>Bone Morphogenetic Protein 2 - metabolism</subject><subject>Conserved Sequence</subject><subject>ELAV-Like Protein 1 - metabolism</subject><subject>GENE REGULATION</subject><subject>GROWTH FACTOR</subject><subject>HeLa Cells</subject><subject>Heterogeneous-Nuclear Ribonucleoprotein D - genetics</subject><subject>Heterogeneous-Nuclear Ribonucleoprotein D - metabolism</subject><subject>Humans</subject><subject>MESENCHYMAL CELL</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Mice</subject><subject>MicroRNAs - genetics</subject><subject>Molecular Sequence Data</subject><subject>POST-TRANSCRIPTIONAL</subject><subject>RNA Interference</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFv1DAQhS0EokvhwB9AlriUQ9qxY8fOBYmN6NKqSwsClQuyEme6m20SBztb2H9f0y0r4NSTR5rvjd7zI-Qlg0MGwI9WtjrkkufwiEwY5CoRmRCPyQRUCglPGd8jz0JYAUCep_wp2eMZZ1wBn5DvhesGHJt-QT_j4DGE5gbpcWlH5wMtXD9619Kp65HOnR-WboF9xC298G7EpqecHkznF_wNjfMcA_Z2uenKlhbYtuE5eXJVtgFf3L_75Ovx-y_Fh-TsfHZSvDtLrNAASZppVkMmpZIsz4XKUNaCWcUkr5i1MeIVQGYl2ForXuYWKp3biqsKVS10ne6Tt9u7w7rqsLYYbZetGXzTlX5jXNmYfzd9szQLd2NEzlKlRTxwcH_Aux9rDKPpmmBjhLJHtw6GKQ2SyejoAWgGWmZa84i-_g9dubXv409EKoblwASL1Ku_ze9c_ykpAkdb4GfT4ma3Z2B-t29i--aufXNaTO-GqEi2iiaM-GunKP21yVSqpLn8ODPfZnB5qvgnM01vASzIrmk</recordid><startdate>201602</startdate><enddate>201602</enddate><creator>Fotinos, Anastasios</creator><creator>Fritz, David T.</creator><creator>Lisica, Steven</creator><creator>Liu, Yijun</creator><creator>Rogers, Melissa B.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201602</creationdate><title>Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in Mesenchymal Cells</title><author>Fotinos, Anastasios ; Fritz, David T. ; Lisica, Steven ; Liu, Yijun ; Rogers, Melissa B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4800-3681d065575199476e5d41c7152b1cc002f006c50cd872a9c0b89cb27be7d48d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>3' Untranslated Regions</topic><topic>Animals</topic><topic>AU Rich Elements</topic><topic>Base Sequence</topic><topic>Binding, Competitive</topic><topic>Bone Morphogenetic Protein 2 - genetics</topic><topic>Bone Morphogenetic Protein 2 - metabolism</topic><topic>Conserved Sequence</topic><topic>ELAV-Like Protein 1 - metabolism</topic><topic>GENE REGULATION</topic><topic>GROWTH FACTOR</topic><topic>HeLa Cells</topic><topic>Heterogeneous-Nuclear Ribonucleoprotein D - genetics</topic><topic>Heterogeneous-Nuclear Ribonucleoprotein D - metabolism</topic><topic>Humans</topic><topic>MESENCHYMAL CELL</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Mice</topic><topic>MicroRNAs - genetics</topic><topic>Molecular Sequence Data</topic><topic>POST-TRANSCRIPTIONAL</topic><topic>RNA Interference</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fotinos, Anastasios</creatorcontrib><creatorcontrib>Fritz, David T.</creatorcontrib><creatorcontrib>Lisica, Steven</creatorcontrib><creatorcontrib>Liu, Yijun</creatorcontrib><creatorcontrib>Rogers, Melissa B.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fotinos, Anastasios</au><au>Fritz, David T.</au><au>Lisica, Steven</au><au>Liu, Yijun</au><au>Rogers, Melissa B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in Mesenchymal Cells</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J. Cell. Biochem</addtitle><date>2016-02</date><risdate>2016</risdate><volume>117</volume><issue>2</issue><spage>439</spage><epage>447</epage><pages>439-447</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>ABSTRACT
The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3′untranslated region (3′UTR) contains a highly conserved AU‐rich element (ARE) embedded in a sequence that commonly represses gene expression in mesenchymal cells. Computational analyses indicate that this site also may bind several microRNAs (miRNAs). Although miRNAs frequently target AU‐rich regions, this ARE is unusual because the miRNAs directly span the ARE. We began to characterize the factors that may regulate Bmp2 expression via this complex site. The activating protein HuR (Hu antigen R, ELAVL1, HGNC:3312) directly binds this ARE and can activate gene expression. An miRNA was demonstrated to reverse HuR‐mediated activation. Mutational and RNA‐interference evidence also supports an AUF1 (AU‐factor‐1, HNRNPD, HGNC:5036) contribution to the observed repressive activity of the 3′UTR in mesenchymal cells. A limited number of studies describe how miRNAs interact with ARE‐binding proteins that bind adjacent sites. This study is among the first to describe protein/miRNA interactions at the same site. J. Cell. Biochem. 117: 439–447, 2016. © 2015 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>26212702</pmid><doi>10.1002/jcb.25290</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3' Untranslated Regions Animals AU Rich Elements Base Sequence Binding, Competitive Bone Morphogenetic Protein 2 - genetics Bone Morphogenetic Protein 2 - metabolism Conserved Sequence ELAV-Like Protein 1 - metabolism GENE REGULATION GROWTH FACTOR HeLa Cells Heterogeneous-Nuclear Ribonucleoprotein D - genetics Heterogeneous-Nuclear Ribonucleoprotein D - metabolism Humans MESENCHYMAL CELL Mesenchymal Stromal Cells - metabolism Mice MicroRNAs - genetics Molecular Sequence Data POST-TRANSCRIPTIONAL RNA Interference |
| title | Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in Mesenchymal Cells |
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