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  1. Article: HuR as a negative posttranscriptional modulator in inflammation.

    Katsanou, Vicky / Papadaki, Olympia / Milatos, Stavros / Blackshear, Perry J / Anderson, Paul / Kollias, George / Kontoyiannis, Dimitris L

    Molecular cell

    2005  Volume 19, Issue 6, Page(s) 777–789

    Abstract: HuR is an RNA binding protein with an alleged role in the posttranscriptional activation of inflammatory mRNAs bearing AU-rich elements (AREs). Here, we show that the inducible increase of HuR in murine innate compartments suppresses inflammatory ... ...

    Abstract HuR is an RNA binding protein with an alleged role in the posttranscriptional activation of inflammatory mRNAs bearing AU-rich elements (AREs). Here, we show that the inducible increase of HuR in murine innate compartments suppresses inflammatory responses in vivo. In macrophages, HuR overexpression induced the translational silencing of specific cytokine mRNAs despite positive or nominal effects on their corresponding turnover. By using a model system of ARE dysfunction, we demonstrate that HuR does not alter the accumulation of target mRNAs in the absence of the destabilizing functions of Tristetraprolin but synergizes with the translational silencer TIA-1 to reduce the translation of cytokine mRNAs. Our data suggest that HuR acts in a pleiotropic fashion in inflammation through its functional interactions with specific mRNA subsets and negative posttranscriptional modules.
    MeSH term(s) Animals ; Antigens, Surface/genetics ; Antigens, Surface/metabolism ; Cells, Cultured ; Cytokines/genetics ; Cytokines/immunology ; ELAV Proteins ; ELAV-Like Protein 1 ; Gene Expression Regulation ; Humans ; Inflammation ; Liver/cytology ; Liver/immunology ; Macrophages/cytology ; Macrophages/immunology ; Mice ; Mice, Transgenic ; Protein Biosynthesis ; RNA Stability ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism
    Chemical Substances Antigens, Surface ; Cytokines ; ELAV Proteins ; ELAV-Like Protein 1 ; ELAVL1 protein, human ; RNA, Messenger ; RNA-Binding Proteins
    Language English
    Publishing date 2005-09-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2005.08.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The RNA-binding protein Elavl1/HuR is essential for placental branching morphogenesis and embryonic development.

    Katsanou, Vicky / Milatos, Stavros / Yiakouvaki, Anthie / Sgantzis, Nikos / Kotsoni, Anastasia / Alexiou, Maria / Harokopos, Vaggelis / Aidinis, Vassilis / Hemberger, Myriam / Kontoyiannis, Dimitris L

    Molecular and cellular biology

    2009  Volume 29, Issue 10, Page(s) 2762–2776

    Abstract: HuR is an RNA-binding protein implicated in a diverse array of pathophysiological processes due to its effects on the posttranscriptional regulation of AU- and U-rich mRNAs. Here we reveal HuR's requirement in embryonic development through its genetic ... ...

    Abstract HuR is an RNA-binding protein implicated in a diverse array of pathophysiological processes due to its effects on the posttranscriptional regulation of AU- and U-rich mRNAs. Here we reveal HuR's requirement in embryonic development through its genetic ablation. Obligatory HuR-null embryos exhibited a stage retardation phenotype and failed to survive beyond midgestation. By means of conditional transgenesis, we restricted HuR's mutation in either embryonic or endothelial compartments to demonstrate that embryonic lethality is consequent to defects in extraembryonic placenta. HuR's absence impaired the invagination of allantoic capillaries into the chorionic trophoblast layer and the differentiation of syncytiotrophoblast cells that control the morphogenesis and vascularization of the placental labyrinth and fetal support. HuR-null embryos rescued from these placental defects proceeded to subsequent developmental stages but displayed defects in skeletal ossification, fusions in limb elements, and asplenia. By coupling gene expression measurements, data meta-analysis, and HuR-RNA association assays, we identified transcription and growth factor mRNAs controlled by HuR, primarily at the posttranscriptional level, to guide morphogenesis, specification, and patterning. Collectively, our data demonstrate the dominant role of HuR in organizing gene expression programs guiding placental labyrinth morphogenesis, skeletal specification patterns, and splenic ontogeny.
    MeSH term(s) Animals ; Antigens, Surface/genetics ; Antigens, Surface/metabolism ; Cells, Cultured ; ELAV Proteins ; ELAV-Like Protein 1 ; Female ; Gene Expression Regulation, Developmental ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Morphogenesis ; Musculoskeletal Abnormalities/genetics ; Musculoskeletal Abnormalities/pathology ; Phenotype ; Placenta/anatomy & histology ; Placenta/embryology ; Pregnancy ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Spleen/abnormalities ; Spleen/embryology
    Chemical Substances Antigens, Surface ; ELAV Proteins ; ELAV-Like Protein 1 ; ELAVL1 protein, human ; RNA, Messenger ; RNA-Binding Proteins
    Language English
    Publishing date 2009-03-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.01393-08
    Database MEDical Literature Analysis and Retrieval System OnLINE

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