The Structure of the C-Terminal KH Domains of KSRP Reveals a Noncanonical Motif Important for mRNA Degradation

María Flor García-Mayoral, David Hollingworth, Laura Masino, Irene Díaz-Moreno, Geoff Kelly, Roberto Gherzi, Chu Fang Chou, Ching Yi Chen, Andres Ramos

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)485-498
Number of pages14
JournalStructure
Volume15
Issue number4
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Protein Splicing
RNA Stability
AU Rich Elements
RNA-Binding Proteins
Cell Proliferation
RNA
Messenger RNA
Proteins

Keywords

  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

García-Mayoral, M. F., Hollingworth, D., Masino, L., Díaz-Moreno, I., Kelly, G., Gherzi, R., ... Ramos, A. (2007). The Structure of the C-Terminal KH Domains of KSRP Reveals a Noncanonical Motif Important for mRNA Degradation. Structure, 15(4), 485-498. https://doi.org/10.1016/j.str.2007.03.006

The Structure of the C-Terminal KH Domains of KSRP Reveals a Noncanonical Motif Important for mRNA Degradation. / García-Mayoral, María Flor; Hollingworth, David; Masino, Laura; Díaz-Moreno, Irene; Kelly, Geoff; Gherzi, Roberto; Chou, Chu Fang; Chen, Ching Yi; Ramos, Andres.

In: Structure, Vol. 15, No. 4, 04.2007, p. 485-498.

Research output: Contribution to journalArticle

García-Mayoral, MF, Hollingworth, D, Masino, L, Díaz-Moreno, I, Kelly, G, Gherzi, R, Chou, CF, Chen, CY & Ramos, A 2007, 'The Structure of the C-Terminal KH Domains of KSRP Reveals a Noncanonical Motif Important for mRNA Degradation', Structure, vol. 15, no. 4, pp. 485-498. https://doi.org/10.1016/j.str.2007.03.006
García-Mayoral, María Flor ; Hollingworth, David ; Masino, Laura ; Díaz-Moreno, Irene ; Kelly, Geoff ; Gherzi, Roberto ; Chou, Chu Fang ; Chen, Ching Yi ; Ramos, Andres. / The Structure of the C-Terminal KH Domains of KSRP Reveals a Noncanonical Motif Important for mRNA Degradation. In: Structure. 2007 ; Vol. 15, No. 4. pp. 485-498.
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