Journal Article

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

Wen-Juan Wei, Shi-Rong Mu, Monika Heiner, Xing Fu, Li-Juan Cao, Xiu-Feng Gong, Albrecht Bindereif and Jingyi Hui

in Nucleic Acids Research

Volume 40, issue 17, pages 8622-8636
Published in print September 2012 | ISSN: 0305-1048
Published online June 2012 | e-ISSN: 1362-4962 | DOI: http://dx.doi.org/10.1093/nar/gks579

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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.

Journal Article.  8631 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology

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