K homology domains of the mouse polycystic kidney disease-related protein, Bicaudal-C (Bicc1), mediate RNA binding in vitro
K homology domains of the mouse polycystic kidney disease-related protein, Bicaudal-C (Bicc1), mediate RNA binding in vitro
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DOI：
10.1159/000112913
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Bryda, Elizabeth C.
中科院分区：
文献类型：
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作者：
Bouvrette, Denise J.;Price, Sarah J.;Bryda, Elizabeth C.
背景/目的：小鼠 Bicc1 (mBicc1) 基因是果蝇 Bicaudal-C (Bic-C) 基因的直系同源物。虽然 Bicc1 在小鼠中的作用尚不清楚，但小鼠 Bicc1 基因的突变与多囊肾病 (PKD) 相关。 mBicc1 蛋白包含三个 K 同源 (KH) 结构域。来自其他含有 KH 结构域的蛋白质以及涉及果蝇和非洲爪蟾 Bic-C 的研究的证据表明，该基序在与 RNA 的相互作用中非常重要。方法：使用 RNA 结合测定来测试小鼠 Bicc1 是否在体外结合同质核糖聚合物。使用一系列编码 mBicc1 蛋白不同区域的构建体来确定 mBicc1 蛋白的哪些区域对于体外 RNA 结合很重要。结果：小鼠 Bicc1 在体外结合同质核糖聚合物，第三个 KH 结构域对于体外 RNA 结合是必要且充分的。 jcpk 小鼠模型中导致 PKD 的突变导致蛋白质无法在体外结合 RNA。结论：本研究表明，小鼠 Bicc1（一种与 PKD 相关的蛋白质）具有体外结合 RNA 的能力。这种结合能力的破坏可能是携带 mBicc1 基因突变的动物中囊肿形成的原因。版权所有 (c) 2008 S. Karger AG，巴塞尔。
Background/Aims: The mouse Bicc1 (mBicc1) gene is the orthologue of the Drosophila Bicaudal-C (Bic-C) gene. While the role of Bicc1 in the mouse is unknown, mutations in the mouse Bicc1 gene are associated with polycystic kidney disease (PKD). The mBicc1 protein contains three K homology (KH) domains. Evidence from other KH domain-containing proteins as well as studies involving both Drosophila and Xenopus Bic-C, suggest that this motif is important in interactions with RNA. Methods: RNA-binding assays were used to test whether mouse Bicc1 binds homoribopolymers in vitro. A series of constructs coding for different regions of the mBicc1 protein were used to determine which regions of the mBicc1 protein were important for in vitro RNA binding. Results: Mouse Bicc1 binds homoribopolymers in vitro and the third KH domain is necessary and sufficient for in vitro RNA binding. The mutation responsible for PKD in the jcpk mouse model results in a protein that is incapable of binding RNA in vitro. Conclusions: This study demonstrates that mouse Bicc1, a protein associated with PKD, has the ability to bind RNA in vitro. Disruption of this binding capability may be responsible for cyst formation in animals carrying mutations in the mBicc1 gene. Copyright (c) 2008 S. Karger AG, Basel.