西亚试剂：：YB-1 binds to CAUC motifs and stimulates exon

Wen-Juan Wei1， Shi-Rong Mu1， Monika Heiner1， Xing Fu1， Li-Juan Cao1， Xiu-Feng Gong1， Albrecht Bindereif2 and Jingyi Hui1，*

Abstract

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.