YB-1 binds to CAUC motifs and stimulates exon inclusion by enhancing the recruitment of U2AF to weak polypyrimidine tracts
Open accessAbstract
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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Computational analysis suggested that the miR-140-5p-G seed in the Ago2 complex and the RBP Ybx1 potentially compete for the same RNA binding sites.
“Computational analysis suggested that the miR-140-5p-G seed in the Ago2 complex and the RBP, Ybx1 (also known as YB-1), potentially compete for the same RNA binding sites”
From Gain-of-function mutation of microRNA-140 in human skeletal dysplasia (2019) · cites this paper as [31]
The Results section (page unavailable) identifies CAUC and CACC as high-affinity RNA-binding motifs for YB-1, supporting the premise that YB-1 binds specific RNA sites. The paper does not report a miR-140-5p-G seed, an Ago2 complex, or computational evidence that either competes with YB-1 for the same sites. (LLM, conf=0.84)
Experimental — accuracy not yet measuredYbx1 seCLIP analysis identified a binding motif similar to the Ybx1 binding motif reported previously.
“Next, Ybx1 seCLIP analysis identified a binding motif similar to the Ybx1 binding motif reported previously30–32”
From Gain-of-function mutation of microRNA-140 in human skeletal dysplasia (2019) · cites this paper as [31]
SRSF3 and YB-1 promote exon inclusion during alternative splicing.
“Interestingly, SRSF3 (43) and YB-1 (44) have also been shown to specifically promote exon inclusion during alternative splicing.”
From Discovery of a Novel CIP2A Variant (NOCIVA) with Clinical Relevance in Predicting TKI Resistance in Myeloid Leukemias (2021) · cites this paper as [44]
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Gain-of-function mutation of microRNA-140 in human skeletal dysplasia
Grigelioniene, G., Suzuki, H. I., Taylan, F., Mirzamohammadi, F., Borochowitz, Z. U., Ayturk, U. M., Tzur, S., Horemuzova, E., Lindstrand, A., Weis, M. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0353-2 · Cited by 103 · see citing works
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- Authors
- Wei, W.-J., Mu, S.-R., Heiner, M., Fu, X., Cao, L.-J., Gong, X.-F., Bindereif, A., & Hui, J.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Hui, Jingyi
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-06-21
- Volume
- 40
- Issue
- 17
- Pages
- 8622-8636
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3458536
- OpenAlex
- W1977846760
- Cited by
- 124
- References
- 52
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 4 · 2023: 10 · 2022: 24 · 2021: 17 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 10 · 2013: 5 · 2012: 1
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- University of Occupational and Environmental Health
- National Natural Science Foundation of China (30970620)
- Chinese Academy of Sciences
- Civil Aviation University of China
- Université de Genève
- University of California, San Diego
- National Key Research and Development Program of China (2011CB811304, 2011CBA01105)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- YB-1, alternative splicing, exon inclusion, U2AF65, polypyrimidine tract, CD44, splicing enhancers, protein-protein interaction, spliceosome
- MeSH terms
- Splicing Factor U2AF, Binding Sites, DNA-Binding Proteins, Exons, Humans, Introns, Nuclear Proteins, Ribonucleoproteins, RNA, RNA Precursors, RNA, Messenger, RNA-Binding Proteins, Alternative Splicing, Hyaluronan Receptors, Drosophila Proteins, Y-Box-Binding Protein 1, SELEX Aptamer Technique, Protein Interaction Domains and Motifs, HEK293 Cells, Nucleotide Motifs
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