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

被引：106

作者：

Tran, Uyen ^{[1
]}

Zakin, Lise ^{[3
]}

Schweickert, Axel ^{[4
]}

Agrawal, Raman ^{[1
]}

Doeger, Remziye ^{[1
]}

Blum, Martin ^{[4
]}

De Robertis, E. M. ^{[3
]}

Wessely, Oliver ^{[1
,2
]}

机构：

[1] Louisiana State Univ, Hlth Sci Ctr, Dept Cell Biol & Anat, New Orleans, LA 70112 USA

[2] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 70112 USA

[3] Univ Calif Los Angeles, Dept Biol Chem, HHMI, Los Angeles, CA 90024 USA

[4] Univ Hohenheim, Inst Zool, D-70593 Stuttgart, Germany

来源：

DEVELOPMENT | 2010年 / 137卷 / 07期

关键词：

P-bodies; Polycystic kidney disease; microRNA; Pronephros; Translational regulation; Mouse; Xenopus; MATERNAL MESSENGER-RNA; POLY(A) POLYMERASE; STRESS GRANULES; DOMAIN PROTEIN; GENE; DISEASE; ENCODES; MECHANISMS; EXPRESSION; TRANSLATION;

D O I：

10.1242/dev.046045

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1107 / 1116

页数：10

共 60 条

[1] The miR-30 miRNA family regulates Xenopus pronephros development and targets the transcription factor Xlim1/Lhx1 [J].

Agrawal, Raman ;

Tran, Uyen ;

Wessely, Oliver .

DEVELOPMENT, 2009, 136 (23) :3927-3936

[2] Stress granules: The Tao of RNA triage [J].

Anderson, Paul ;

Kedersha, Nancy .

TRENDS IN BIOCHEMICAL SCIENCES, 2008, 33 (03) :141-150

[3] Ciliation and gene expression distinguish between node and posterior notochord in the mammalian embryo [J].

Blum, Martin ;

Andre, Philipp ;

Muders, Kerstin ;

Schweickert, Axel ;

Fischer, Anja ;

Bitzer, Eva ;

Bogusch, Susanne ;

Beyer, Tina ;

van Straaten, Henny W. M. ;

Viebahn, Christoph .

DIFFERENTIATION, 2007, 75 (02) :133-146

[4] ANALYSIS OF THE GENOMIC SEQUENCE FOR THE AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE (PKD1) GENE PREDICTS THE PRESENCE OF A LEUCINE-RICH REPEAT [J].

BURN, TC ;

CONNORS, TD ;

DACKOWSKI, WR ;

PETRY, LR ;

VANRAAY, TJ ;

MILLHOLLAND, JM ;

VENET, M ;

MILLER, G ;

HAKIM, RM ;

LANDES, GM ;

KLINGER, KW ;

FENG, Q ;

ONUCHIC, LF ;

WATNICK, T ;

GERMINO, GG ;

DOGGETT, NA .

HUMAN MOLECULAR GENETICS, 1995, 4 (04) :575-582

[5] Cytoplasmic polyadenylation element (CPE)- and CPE-binding protein (CPEB)-independent mechanisms regulate early class maternal mRNA translational activation in Xenopus oocytes [J].

Charlesworth, A ;

Cox, LL ;

MacNicol, AM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (17) :17650-17659

[6] Bicaudal-C recruits CCR4-NOT deadenylase to target mRNAs and regulates oogenesis, cytoskeletal organization, and its own expression [J].

Chicoine, Jarred ;

Benoit, Perrine ;

Gamberi, Chiara ;

Paliouras, Miltiadis ;

Simonelig, Martine ;

Lasko, Paul .

DEVELOPMENTAL CELL, 2007, 13 (05) :691-704

[7] The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition [J].

Cloonan, Nicole ;

Brown, Mellissa K. ;

Steptoe, Anita L. ;

Wani, Shivangi ;

Chan, Wei Ling ;

Forrest, Alistair Rr ;

Kolle, Gabriel ;

Gabrielli, Brian ;

Grimmond, Sean M. .

GENOME BIOLOGY, 2008, 9 (08)

[8] Positional cloning of jcpk/bpk locus of the mouse [J].

Cogswell, C ;

Price, SJ ;

Hou, XY ;

Guay-Woodford, LM ;

Flaherty, L ;

Bryda, EC .

MAMMALIAN GENOME, 2003, 14 (04) :242-249

[9] The cellular basis of kidney development [J].

Dressler, Gregory R. .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2006, 22 :509-529

[10] Kidney development and disease in the zebrafish [J].

Drummond, IA .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (02) :299-304

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