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  • The Company of Biologists  (3)
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  • The Company of Biologists  (3)
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  • 1
    In: Journal of Cell Science, The Company of Biologists, Vol. 123, No. 7 ( 2010-04-01), p. e1-e1
    Type of Medium: Online Resource
    ISSN: 1477-9137 , 0021-9533
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2010
    detail.hit.zdb_id: 219171-4
    detail.hit.zdb_id: 1483099-1
    SSG: 12
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  • 2
    In: Development, The Company of Biologists, Vol. 137, No. 7 ( 2010-04-01), p. 1107-1116
    Abstract: The RNA-binding protein Bicaudal C is an important regulator of embryonic development in C. elegans, Drosophila and Xenopus. In mouse, bicaudal C (Bicc1) mutants are characterized by the formation of fluid-filled cysts in the kidney and by expansion of epithelial ducts in liver and pancreas. This phenotype is reminiscent of human forms of polycystic kidney disease (PKD). Here, we now provide data that Bicc1 functions by modulating the expression of polycystin 2 (Pkd2), a member of the transient receptor potential (TRP) superfamily. Molecular analyses demonstrate that Bicc1 acts as a post-transcriptional regulator upstream of Pkd2. It regulates the stability of Pkd2 mRNA and its translation efficiency. Bicc1 antagonized the repressive activity of the miR-17 microRNA family on the 3′UTR of Pkd2 mRNA. This was substantiated in Xenopus, in which the pronephric defects of bicc1 knockdowns were rescued by reducing miR-17 activity. At the cellular level, Bicc1 protein is localized to cytoplasmic foci that are positive for the P-body markers GW182 and HEDLs. Based on these data, we propose that the kidney phenotype in Bicc1−/− mutant mice is caused by dysregulation of a microRNA-based translational control mechanism.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2010
    detail.hit.zdb_id: 2007916-3
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    The Company of Biologists ; 2009
    In:  Development Vol. 136, No. 23 ( 2009-12-01), p. 3927-3936
    In: Development, The Company of Biologists, Vol. 136, No. 23 ( 2009-12-01), p. 3927-3936
    Abstract: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. They are involved in diverse biological processes, such as development, differentiation, cell proliferation and apoptosis. To study the role of miRNAs during pronephric kidney development of Xenopus, global miRNA biogenesis was eliminated by knockdown of two key components: Dicer and Dgcr8. These embryos developed a range of kidney defects, including edema formation, delayed renal epithelial differentiation and abnormal patterning. To identify a causative miRNA, mouse and frog kidneys were screened for putative candidates. Among these, the miR-30 family showed the most prominent kidney-restricted expression. Moreover, knockdown of miR-30a-5p phenocopied most of the pronephric defects observed upon global inhibition of miRNA biogenesis. Molecular analyses revealed that miR-30 regulates the LIM-class homeobox factor Xlim1/Lhx1, a major transcriptional regulator of kidney development. miR-30 targeted Xlim1/Lhx1 via two previously unrecognized binding sites in its 3′UTR and thereby restricted its activity. During kidney development, Xlim1/Lhx1 is required in the early stages, but is downregulated subsequently. However, in the absence of miR-30 activity, Xlim1/Lhx1 is maintained at high levels and, therefore, may contribute to the delayed terminal differentiation of the amphibian pronephros.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2009
    detail.hit.zdb_id: 2007916-3
    SSG: 12
    Location Call Number Limitation Availability
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