Bicc1 links the regulation of cAMP signaling in polycystic kidneys to microRNA-induced gene silencing.

Details

Serval ID
serval:BIB_31B576077D22
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bicc1 links the regulation of cAMP signaling in polycystic kidneys to microRNA-induced gene silencing.
Journal
Journal of Molecular Cell Biology
Author(s)
Piazzon N., Maisonneuve C., Guilleret I., Rotman S., Constam D.B.
ISSN
1759-4685 (Electronic)
ISSN-L
1759-4685
Publication state
Published
Issued date
2012
Volume
4
Number
6
Pages
398-408
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Genetic defects in autosomal-dominant polycystic kidney disease (ADPKD) promote cystic growth of renal tubules, at least in part by stimulating the accumulation of cAMP. How renal cAMP levels are regulated is incompletely understood. We show that cAMP and the expression of its synthetic enzyme adenylate cyclase-6 (AC6) are up-regulated in cystic kidneys of Bicc1(-)(/-) knockout mice. Bicc1, a protein comprising three K homology (KH) domains and a sterile alpha motif (SAM), is expressed in proximal tubules. The KH domains independently bind AC6 mRNA and recruit the miR-125a from Dicer, whereas the SAM domain enables silencing by Argonaute and TNRC6A/GW182. Bicc1 similarly induces silencing of the protein kinase inhibitor PKIα by miR-27a. Thus, Bicc1 is needed on these target mRNAs for silencing by specific miRNAs. The repression of AC6 by Bicc1 might explain why cysts in ADPKD patients preferentially arise from distal tubules.
Pubmed
Web of science
Open Access
Yes
Create date
31/01/2013 19:20
Last modification date
20/08/2019 14:17
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