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 language | English |
|---|---|
| Pages (from-to) | 485-498 |
| Number of pages | 14 |
| Journal | Structure |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2007 |
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Keywords
- RNA
ASJC Scopus subject areas
- Molecular Biology
- Structural Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - The Structure of the C-Terminal KH Domains of KSRP Reveals a Noncanonical Motif Important for mRNA Degradation
AU - García-Mayoral, María Flor
AU - Hollingworth, David
AU - Masino, Laura
AU - Díaz-Moreno, Irene
AU - Kelly, Geoff
AU - Gherzi, Roberto
AU - Chou, Chu Fang
AU - Chen, Ching Yi
AU - Ramos, Andres
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - RNA
UR - http://www.scopus.com/inward/record.url?scp=34047269428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047269428&partnerID=8YFLogxK
U2 - 10.1016/j.str.2007.03.006
DO - 10.1016/j.str.2007.03.006
M3 - Article
C2 - 17437720
AN - SCOPUS:34047269428
VL - 15
SP - 485
EP - 498
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 4
ER -