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

被引：45

作者：

Piazzon, Nathalie ^{[1
]}

Maisonneuve, Charlotte ^{[1
]}

Guilleret, Isabelle ^{[1
]}

Rotman, Samuel ^{[2
]}

Constam, Daniel B. ^{[1
]}

机构：

[1] EPFL SV ISREC, CH-1015 Lausanne, Switzerland

[2] CHU Vaudois, Inst Pathol, CH-1011 Lausanne, Switzerland

来源：

JOURNAL OF MOLECULAR CELL BIOLOGY | 2012年 / 4卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

PKD; proximal tubules; bicaudal-C; cyclic AMP; PKA; PKI; miRNA; RNA-BINDING PROTEIN; CYST EPITHELIAL-CELLS; P-BODY FORMATION; AUTOSOMAL-DOMINANT; BICAUDAL-C; CCR4-NOT DEADENYLASE; GW182; PROTEINS; PRIMARY CILIUM; MOUSE MODEL; DISEASE;

D O I：

10.1093/jmcb/mjs027

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 PKI 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.

引用

页码：398 / 408

页数：11

共 67 条

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