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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2146-2153. Prepublished online as a Blood First Edition Paper on November 2, 2004; DOI 10.1182/blood-2004-05-1757. This Article Full Text (PDF) All Versions of this Article: 2004-05-1757v1 105/5/2146    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yang, G. Articles by Benz Jr., E. J Search for Related Content PubMed PubMed Citation Articles by Yang, G. Articles by Benz Jr., E. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 6, 2004 Accepted October 9, 2004 An erythroid differentiation-specific splicing switch in protein 4.1R mediated by the interaction of SF2/ASF with an exonic splicing enhancer Guang Yang, Shu-Ching Huang*, Jane Y Wu, and Edward J Benz Jr. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Brigham and Women's Hospital, Boston, MA, USA * Corresponding author; email: shu-ching_huang{at}dfci.harvard.edu. Protein 4.1R is a vital component of the red blood cell membrane cytoskeleton. Promotion of cytoskeletal junctional complex stability requires an erythroid differentiation stage specific splicing switch promoting inclusion of exon 16 within the spectrin/actin binding domain. We showed earlier that an intricate combination of positive and negative RNA elements controls exon 16 splicing. In this report, we further identified three putative exonic splicing enhancers within exon 16 and investigated the function of the sequence CAGACAT in the regulation of exon 16 splicing. Mutation of these sequences leads to increased exclusion of exon 16 in both in vivo and in vitro splicing assays, indicating that CAGACAT is a functional exonic splicing enhancer. UV cross-linking further detects a ~33 kD protein that specifically binds to the CAGACAT-containing transcript. An anti-SF2/ASF antibody specifically immunoprecipitates the ~33 kD protein. Furthermore, SF2/ASF stimulates exon 16 inclusion in both in vitro complementation assays and minigene-transfected mouse erythroleukemia cells (MELC). Finally, SF2/ASF expression is upregulated and correlates with exon 16 inclusion in differentiated MELC. These results suggest that increased SF2/ASF expression in differentiated mouse erythroleukemia mediates a differentiation stage specific exon 16 splicing switch through its interaction with the exonic splicing enhancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S.-C. Huang, A. Cho, S. Norton, E. S. Liu, J. Park, A. Zhou, I. D. Munagala, A. C. Ou, G. Yang, A. Wickrema, et al. Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5' exons of protein 4.1R gene Blood, November 5, 2009; 114(19): 4233 - 4242. [Abstract] [Full Text] [PDF] M. L. Yamamoto, T. A. Clark, S. L. Gee, J.-A. Kang, A. C. Schweitzer, A. Wickrema, and J. G. Conboy Alternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis Blood, April 2, 2009; 113(14): 3363 - 3370. [Abstract] [Full Text] [PDF] A. Zhou, A. C. Ou, A. Cho, E. J. Benz Jr., and S.-C. Huang Novel Splicing Factor RBM25 Modulates Bcl-x Pre-mRNA 5' Splice Site Selection Mol. Cell. Biol., October 1, 2008; 28(19): 5924 - 5936. [Abstract] [Full Text] [PDF] G. Grech, M. Blazquez-Domingo, A. Kolbus, W. J. Bakker, E. W. Mullner, H. Beug, and M. von Lindern Igbp1 is part of a positive feedback loop in stem cell factor-dependent, selective mRNA translation initiation inhibiting erythroid differentiation Blood, October 1, 2008; 112(7): 2750 - 2760. [Abstract] [Full Text] [PDF] G. Yang, S.-C. Huang, J. Y. Wu, and E. J. Benz Jr Regulated Fox-2 isoform expression mediates protein 4.1R splicing during erythroid differentiation Blood, January 1, 2008; 111(1): 392 - 401. [Abstract] [Full Text] [PDF] E. Wang, N. Dimova, and F. Cambi PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytes Nucleic Acids Res., June 12, 2007; (2007) gkm387v1. [Abstract] [Full Text] [PDF] J. L. Chisa and D. T. Burke Mammalian mRNA Splice-Isoform Selection Is Tightly Controlled Genetics, March 1, 2007; 175(3): 1079 - 1087. [Abstract] [Full Text] [PDF] C. Guillouf, I. Gallais, and F. Moreau-Gachelin Spi-1/PU.1 Oncoprotein Affects Splicing Decisions in a Promoter Binding-dependent Manner J. Biol. Chem., July 14, 2006; 281(28): 19145 - 19155. [Abstract] [Full Text] [PDF] J. L. Ponthier, C. Schluepen, W. Chen, R. A. Lersch, S. L. Gee, V. C. Hou, A. J. Lo, S. A. Short, J. A. Chasis, J. C. Winkelmann, et al. Fox-2 Splicing Factor Binds to a Conserved Intron Motif to Promote Inclusion of Protein 4.1R Alternative Exon 16 J. Biol. Chem., May 5, 2006; 281(18): 12468 - 12474. [Abstract] [Full Text] [PDF]

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