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

García-Mayoral, MF; Hollingworth, D; Masino, L; Díaz-Moreno, I; Kelly, G; Gherzi, R; Chou, CF; ... Ramos, A; + view all (2007) The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation. Structure , 15 (4) pp. 485-498. 10.1016/j.str.2007.03.006. Green open access

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Abstract

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.

Type: Article
Title: The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.str.2007.03.006
Publisher version: https://doi.org/10.1016/j.str.2007.03.006
Language: English
Additional information: © 2007 Elsevier Ltd. All rights reserved. Under an Elsevier user license. This is a non commercial license where the use of published articles for commercial purposes is prohibited.
Keywords: Amino Acid Motifs, Amino Acid Sequence, Cell Line, Humans, Molecular Sequence Data, Protein Structure, Tertiary, RNA, Messenger, RNA-Binding Proteins, Trans-Activators
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1418593
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