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The sequence selectivity of KSRP explains its flexibility in the recognition of the RNA targets

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...

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Detalles Bibliográficos
Autores principales: García-Mayoral, María Flor, Díaz-Moreno, Irene, Hollingworth, David, Ramos, Andres
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532734/
https://www.ncbi.nlm.nih.gov/pubmed/18684992
http://dx.doi.org/10.1093/nar/gkn509
Descripción
Sumario: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.