Nucleic Acids Research Advance Access published online on August 6, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn509
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The sequence selectivity of KSRP explains its flexibility in the recognition of the RNA targets
MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
*To whom correspondence should be addressed. Tel: 44 020 88162550; Fax: 44 020 89064477; Email: aramos{at}nimr.mrc.ac.uk
Received May 20, 2008. Revised July 23, 2008. Accepted July 24, 2008.
K-homology (KH) splicing regulator protein (KSRP) is a multi-domain RNA-binding protein that regulates different steps of mRNA metabolism, from mRNA splicing to mRNA decay, interacting with a broad range of RNA sequences. To understand how KSRP recognizes its different RNA targets it is necessary to define the general rules of KSRP–RNA interaction. We describe here a complete scaffold-independent analysis of the RNA-binding potential of the four KH domains of KSRP. The analysis shows that KH3 binds to the RNA with a significantly higher affinity than the other domains and recognizes specifically a G-rich target. It also demonstrates that the other KH domains of KSRP display different sequence preferences explaining the broad range of targets recognized by the protein. Further, KSRP shows a strong negative selectivity for sequences containing several adjacent Cytosines limiting the target choice of KSRP within single-stranded RNA regions. The in-depth analysis of the RNA-binding potential of the KH domains of KSRP provides us with an understanding of the role of low sequence specificity domains in RNA recognition by multi-domain RNA-binding proteins.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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