The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation

被引:99
作者
Garcia-Mayoral, Maria Flor
Hollingworth, David
Masino, Laura
Diaz-Moreno, Irene
Kelly, Geoff
Gherzi, Roberto
Chou, Chu-Fan
Chen, Ching-Yi
Ramos, Andres [1 ]
机构
[1] MRC Natl Inst Med Res, London NW7 1AA, England
[2] MRC Biomol NMR Ctr, London NW7 1AA, England
[3] Ist Nazl Ric Canc, Gene Express Regulat Lab, I-16132 Genoa, Italy
[4] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA
基金
英国医学研究理事会;
关键词
D O I
10.1016/j.str.2007.03.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The AU-rich element (ARE) RNA-binding protein KSRP (K-homology splicing regulator protein) contains four KH domains and promotes the degradation of specific mRNAs; that encode proteins with functions in cellular proliferation and inflammatory response. The fourth KH domain (KH4) is essential for mRNA recognition and decay but requires the third KH domain (KH3) for its function. We show that KH3 and KH4 behave as independent binding modules and can interact with different regions of the AU-rich RNA targets of KSRP. This provides KSRP with the structural flexibility needed to recognize a set of different targets in the context of their 3'UTR structural settings. Surprisingly, we find that KH4 binds to its target AREs with lower affinity than KH3 and that KSRP's mRNA binding, and mRNA degradation activities are closely associated with a conserved structural element of KH4.
引用
收藏
页码:485 / 498
页数:14
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