Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-41260
Development. April 1, 2010; 137 (7): 1107-16.

The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity.

Tran U , Zakin L , Schweickert A , Agrawal R , Döger R , Blum M , De Robertis EM , Wessely O .


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.

PubMed ID: 20215348
PMC ID: PMC2835326
Article link: Development.
Grant support: 1R01DK080745-01A2 NIDDK NIH HHS , 5R21DK070671-03 NIDDK NIH HHS , 5R21DK077763-03 NIDDK NIH HHSHoward Hughes Medical Institute , R01 DK080745-01A2 NIDDK NIH HHS , R21 DK077763-02 NIDDK NIH HHS , R01 HD021502-24 NICHD NIH HHS , R01 HD021502-25 NICHD NIH HHS , R01 DK080745 NIDDK NIH HHS , R01 HD021502 NICHD NIH HHS , R21 DK077763 NIDDK NIH HHS , 5R21DK070671-03 NIDDK NIH HHS , 5R21DK077763-03 NIDDK NIH HHS , 1R01DK080745-01A2 NIDDK NIH HHS , R01 HD021502-24 NICHD NIH HHS , R21 DK077763 NIDDK NIH HHS , R21 DK077763-02 NIDDK NIH HHS , R01 DK080745-01A2 NIDDK NIH HHS , R01 HD021502 NICHD NIH HHSHoward Hughes Medical Institute , R01 DK080745 NIDDK NIH HHS , R21 DK070671 NIDDK NIH HHS

Genes referenced: actl6a bicc1 edc4 lhx1 myc pkd1 pkd2 pkhd1 prkd1 slc12a3 tnrc6a pkd1l2 slc4a4

Morpholinos referenced: btg-x MO1 btg-x MO2 pkd2 MO1

References:
, 1995, Pubmed[+]


Article Images: [+] show captions

My Xenbase: [ Log-in / Register ]
version: [4.5.0]

Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556