YB-1 binds to CAUC motifs and stimulates exon inclusion by enhancing the recruitment of U2AF to weak polypyrimidine tracts.

Authors:
Wen-juan Wei
Wen-juan Wei
China Medical University
China
Monika Heiner
Monika Heiner
Technical University of Applied Sciences Berlin
Germany
Xing Fu
Xing Fu
Tsinghua University
China
Li-Juan Cao
Li-Juan Cao
Jiangsu Institute of Hematology
China
Albrecht Bindereif
Albrecht Bindereif
Institute of Biochemistry
Germany
Jingyi Hui
Jingyi Hui
Justus-Liebig-Universit├Ąt Giessen
Germany

Nucleic Acids Res 2012 Sep 22;40(17):8622-36. Epub 2012 Jun 22.

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China.

The human Y box-binding protein-1 (YB-1) is a deoxyribonucleic acid (DNA)/ribonucleic acid (RNA)-binding protein with pleiotropic functions. Besides its roles in the regulation of transcription and translation, several recent studies indicate that YB-1 is a spliceosome-associated protein and is involved in alternative splicing, but the underlying mechanism has remained elusive. Here, we define both CAUC and CACC as high-affinity binding motifs for YB-1 by systematic evolution of ligands by exponential enrichment (SELEX) and demonstrate that these newly defined motifs function as splicing enhancers. Interestingly, on the endogenous CD44 gene, YB-1 appears to mediate a network interaction to activate exon v5 inclusion via multiple CAUC motifs in both the alternative exon and its upstream polypyrimidine tract. We provide evidence that YB-1 activates splicing by facilitating the recruitment of U2AF65 to weak polypyrimidine tracts through direct protein-protein interactions. Together, these findings suggest a vital role of YB-1 in activating a subset of weak 3' splice sites in mammalian cells.

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Source
http://dx.doi.org/10.1093/nar/gks579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458536PMC

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September 2012
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