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Related Collections Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2001, Vol. 98, No. 13, pp. 3809-3816 RED CELLS Multiple cis elements regulate an alternative splicing event at 4.1R pre-mRNA during erythroid differentiation Mireille Deguillien, Shu-Ching Huang, Madeleine Morinière, Natacha Dreumont, Edward J. Benz Jr, and Faouzi Baklouti From the Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Lyon 1, Villeurbanne, France; Dana-Farber/Harvard Cancer Center and Department of Medicine, Brigham and Women's Hospital, Department of Pediatrics, Children's Hospital of Boston, and Harvard Medical School, Boston, MA. The inclusion of exon 16 in the mature protein 4.1R messenger RNA (mRNA) is a critical event in red blood cell membrane biogenesis. It occurs during late erythroid development and results in inclusion of the 10-kd domain needed for stabilization of the spectrin/actin lattice. In this study, an experimental model was established in murine erythroleukemia cells that reproduces the endogenous exon 16 splicing patterns from a transfected minigene. Exon 16 was excluded in predifferentiated and predominantly included after induction. This suggests that the minigene contained exon and abutting intronic sequences sufficient for splicing regulation. A systematic analysis of the cis-acting regulatory sequences that reside within the exon and flanking introns was performed. Results showed that (1) the upstream intron of 4.1R pre-mRNA is required for exon recognition and it displays 2 enhancer elements, a distal element acting in differentiating cells and a proximal constitutive enhancer that resides within the 25 nucleotides preceding the acceptor site; (2) the exon itself contains a strong constitutive splicing silencer; (3) the exon has a weak 5' splice site; and (4) the downstream intron contains at least 2 splicing enhancer elements acting in differentiating cells, a proximal element at the vicinity of the 5' splice site, and a distal element containing 3 copies of the UGCAUG motif. These results suggest that the interplay between negative and positive elements may determine the inclusion or exclusion of exon 16. The activation of the enhancer elements in late erythroid differentiation may play an important role in the retention of exon 16. © 2001 by The American Society of Hematology.   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] F. Marques-Garcia, N. Ferrandiz, R. Fernandez-Alonso, L. Gonzalez-Cano, M. Herreros-Villanueva, M. Rosa-Garrido, B. Fernandez-Garcia, J. P. Vaque, M. M. Marques, M. E. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020