Alternate modes of cognate RNA recognition by human PUMILIO proteins.

Alternate modes of cognate RNA recognition by human PUMILIO proteins.
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DOI:
10.1016/j.str.2010.12.019
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发表时间:
2011-03-09
期刊:
影响因子:
5.7
通讯作者:
Hall, Traci M. Tanaka
Hall, Traci M. Tanaka
中科院分区:
生物学2区
文献类型:
--
作者:
Lu, Gang;Hall, Traci M. Tanaka

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人PUMILIO 1(PUM 1)和PUMILIO 2(PUM 2)是PUMILIO/FBF(PUF)家族的成员,在转录后调节特定的靶mRNA。最近的研究已经确定了与人类GST 1和GST 2相关的mRNA靶点。在这里,我们通过与四个同源RNA序列(包括来自p38α和erk 2 MAP激酶mRNA的序列)复合的p38α和erk 1和p38 α 2的RNA结合结构域的晶体结构,探索了人PUF蛋白识别天然靶RNA的结构基础。我们观察到三种不同的模式的RNA结合周围的第5个RNA碱基,其中两个是不同的原型1重复:1 RNA碱基结合模式先前确定的模型RNA序列。在体外,不同的结合模式不会显著地影响BMP 1和BMP 2的RNA结合亲和力。然而,这些结合模式产生了结构可变的识别表面,这表明在体内招募由PUF:RNA复合物定义的下游效应蛋白的机制。
Human PUMILIO1 (PUM1) and PUMILIO2 (PUM2) are members of the PUMILIO/FBF (PUF) family that regulate specific target mRNAs posttranscriptionally. Recent studies have identified mRNA targets associated with human PUM1 and PUM2. Here we explore the structural basis of natural target RNA recognition by human PUF proteins through crystal structures of the RNA-binding domains of PUM1 and PUM2 in complex with four cognate RNA sequences including sequences from p38α and erk2 MAP kinase mRNAs. We observe three distinct modes of RNA binding around the 5th RNA base, two of which are different from the prototypical 1 repeat:1 RNA base binding mode previously identified with model RNA sequences. RNA-binding affinities of PUM1 and PUM2 are not affected dramatically by the different binding modes in vitro. However, these modes of binding create structurally variable recognition surfaces that suggest a mechanism in vivo for recruitment of downstream effector proteins defined by the PUF:RNA complex.
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